Golimumab is a TNF-alpha blocker (TNF blocker) available in both intravenous and subcutaneous formulations. Golimumab subcutaneous injections are given once monthly for maintenance treatment. The intravenous infusion is given every 8 weeks for maintenance therapy after therapy induction. As with other TNF blockers, golimumab is efficacious for a variety of inflammatory conditions. Golimumab is indicated for the treatment of patients with moderately to severely active rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and polyarticular juvenile idiopathic arthritis (pJIA). In adults with rheumatoid arthritis (RA) or psoriatic arthritis (PsA), the drug improves clinical signs and symptoms, inhibits the radiographic progression of structural joint damage, and improves physical function; in adults with ankylosing spondylitis (AS), the drug improves clinical signs and symptoms of active disease. For adult RA, golimumab is used with methotrexate. For PsA or AS, subcutaneous golimumab may be with or without methotrexate. Corticosteroids, other non-biologic disease-modifying antirheumatic drugs (DMARDs), and nonsteroidal antiinflammatory drugs (NSAIDs) may be continued with subcutaneous golimumab therapy in patients with RA, PsA, or AS. The ideal combination of therapy for individual patients with inflammatory arthritis conditions is determined by treat to target strategies and severity of disease. For PsA, TNF-blockers are considered a first-line treatment, even in treatment-naive patients. Golimumab is also indicated in adults with moderate to severe ulcerative colitis; the drug induces and maintains symptomatic improvement and clinical remission in responders, improving endoscopic appearance of the mucosa during induction. As with other TNF-alpha blockers, golimumab carries a boxed warning that highlights risk for serious infections and potential malignancy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect the solution for particulate matter or discoloration before administration.
Intravenous Administration
Preparation of Intravenous infusion
-Only the Simponi Aria formulation of golimumab may be administered intravenously.
-The Simponi Aria injection solution in vials should be clear to slightly opalescent and colorless to light yellow. The solution may develop a few fine translucent particles, as golimumab is a protein. Do not use if opaque particles, discoloration, or other foreign particles are present.
-Calculate the number of vials necessary based on the recommended dosage. Each vial contains 50 mg/4 mL of golimumab.
-Do not shake the vials.
-Dilute the total volume of golimumab with 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection to yield a final volume of 100 mL for infusion. Withdraw the volume of diluent from a 100 mL infusion bag or bottle equal to the total volume of golimumab to be added. Slowly add golimumab to the diluent using aseptic technique and gently mix.
-Discard any unused solution remaining in vials.
-Storage: The prepared infusion solution may be stored for up to 4 hours at room temperature.
Intravenous infusion administration
-Prior to intravenous infusion, visually inspect the diluted infusion solution for particulate matter or discoloration. Do not use if these exist.
-Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 0.22 micrometer or less).
-Infuse over 30 minutes.
-Do not infuse concomitantly in the same intravenous line with other agents. No physical biochemical compatibility studies have been conducted to evaluate the use of other intravenous agents in the same intravenous line.
Subcutaneous Administration
-Only the Simponi formulation of golimumab may be administered subcutaneously.
-Simponi injection solution is clear to slightly opalescent and colorless to light yellow. Do not use if the solution is discolored, or cloudy, or if foreign particles are present.
-Do not shake the prefilled syringe or autoinjector.
-Injection sites include the front part of the middle thigh and the lower abdomen (but do not inject within 2 inches of the navel). If administered by another person, the prefilled syringe may be given in the back of the upper arm; do not administer the autoinjector into the arm as this may result in injury or failure of the device.
-Rotate injection sites. Do not administer where skin is tender, bruised, red, or hard.
SmartJect Autoinjector
-Allow the single-use prefilled autoinjector to reach room temperature by removing the product from the refrigerator and allow the device to warm to room temperature for at least 30 minutes before use. Do not warm the autoinjector in any other way (e.g., hot water or microwave).
-Immediately before use, remove cap. Inject golimumab within 5 minutes of cap removal. Do not put the cap back on, as cap replacement may damage the needle. Do not inject if the device has been dropped without the cap on.
-Place the open end of the autoinjector against the injection site at a 90-degree angle. Make sure the green safety sleeve is stable and as flat as possible against the skin. If the device is not stable during the injection, you risk bending the needle.
-Do not pinch the skin to avoid injury, including needlestick injury.
-Press the autoinjector against the skin until the green safety sleeve slides into the clear cover; only the wider part of the green safety sleeve stays outside the clear cover. Do not push the blue button while pressing the green safety sleeve into the clear cover. Pushing the blue button before the safety sleeve slides is pressed down can cause failure of the device.
-Once the safety sleeve slides into the clear cover, press the blue button to start the injection. Listen for an audible, loud first 'click'; do not pull the autoinjector away from the skin. Keep holding the device against the skin while waiting for the second audible 'click'; this usually takes 3 to 6 seconds but may take up to 15 seconds. The second 'click' means the injection is complete and the device can be lifted from the skin. If the autoinjector is pulled away from the skin before the injection is complete, the full dose may not be administered.
-Do not rub the injection site.
-Look at the viewing window. If it is not yellow, call 1-800-526-7736; do not administer a second dose without talking with the prescribing health care provider.
-Properly dispose of the used device.
Prefilled syringe
-Allow the single-use prefilled syringe to reach room temperature by removing the product from the refrigerator and allow to sit at room temperature for at least 30 minutes before use. Do not warm the autoinjector in any other way (e.g., hot water or microwave).
-Immediately before use, remove the needle cover by pulling it straight off; do not twist off or recap. Inject golimumab within 5 minutes of needle cover removal.
-Hold the syringe in one hand like a pencil and use the other hand to gently pinch a fold of skin at the cleaned injection site. Do not touch the plunger or the area above finger flange prior to administration as this may cause the needle safety device to activate.
-Insert the needle at a 45-degree angle to the skin. Inject golimumab by pushing the plunger all the way down until it stops. Release pressure from the plunger. The safety guard will cover the needle and lock into place, removing the needle from the skin.
-Do not rub the injection site.
-Properly dispose of the used prefilled syringe.
Among 1233 patients with ulcerative colitis who received golimumab, no new adverse drug reactions were identified and the frequency of adverse drug reactions was similar to the safety profile observed in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
Golimumab may cause elevated hepatic enzymes. In trials involving patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis that were up to 16 weeks in duration, increased alanine aminotransferase (ALT) concentrations occurred in 4% of 1,659 subcutaneous golimumab recipients at rates higher than with placebo; increased aspartate aminotransferase (AST) concentrations occurred in 3% of golimumab recipients. Elevations of ALT of at least 5 times the upper limit of normal (ULN) were noted in 0.7% of golimumab recipients. Elevations of ALT of at least 3 times the ULN were noted in 2% of patients. In ulcerative colitis studies, 2% of patients receiving subcutaneous golimumab developed ALT elevations 3 times or more times the ULN; rates of ALT elevations 5 times or more times the ULN were similar to placebo. In a psoriatic arthritis trial, ALT elevations occurred in 7.9% and AST elevations in 5.4% of patients receiving IV golimumab. In an ankylosing spondylitis trial 2.9% of those that received IV golimumab experienced ALT elevations. In a 24-week trial of IV golimumab for rheumatoid arthritis, ALT elevations of 3 or more times the ULN occurred in 2.3% and elevations 5 or more times the ULN occurred in 0.8% of patients, while AST elevations occurred in less than 1% of treated patients. In a 24-week psoriatic arthritis study, ALT elevations of at least 5 times the ULN were reported in 1.7% and ALT elevations 3 to less than 5 times the ULN occurred in 2.9% of intravenous golimumab patients compared to less than 1% of placebo patients. The relationship between golimumab receipt and ALT elevation is unclear, as many patients were taking medications that are known to cause liver enzyme elevations. Of importance, reports exist of severe hepatic reactions such as acute hepatic failure in TNF-blocker recipients. Reactivation of hepatitis B virus (HBV) may also occur in patients who are chronic HBV carriers and who take golimumab. Viral reactivation has been fatal in some patients who took TNF-blocker therapy. Most reports of HBV reactivation have been in patients who were taking other medicines that suppress the immune system; immunosuppressant drugs may also contribute to HBV reactivation. Stop golimumab and start effective antiviral therapy in patients who develop HBV reactivation. The safety of resuming golimumab after control of HBV reactivation is achieved is unknown. If golimumab is restarted, carefully monitor patients.
Golimumab, like other TNF-blockers, is associated with a risk for serious infection. In clinical trials, infections were noted in 27% to 28% of golimumab recipients and in 24% to 25% of control-treated recipients. In a phase 2/3 ulcerative colitis clinical trial, the incidence of infection was 12% for both golimumab and placebo patients. Pooled data from phase 3 trials comparing golimumab +/- Disease Modifying Antirheumatic Drugs (DMARD) to placebo +/- DMARD in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis indicated that the following infections were reported in at least 1% of patients in the subcutaneous golimumab/DMARD group and with a higher incidence than the placebo/DMARD group: upper respiratory tract infection (16%), viral infections such as influenza and herpes (5%), bronchitis (2%), superficial fungal infection (2%), and sinusitis (2%). In a trial evaluating the IV formulation of golimumab in rheumatoid arthritis patients, infectious events reported in at least 1% of patients in the golimumab/methotrexate group and with a higher incidence than placebo treated patients included upper respiratory tract infection (13%), viral infections such as influenza and herpes (4%), bacterial infections (1%), and bronchitis (3%). Sinusitis was reported in less than 1% of golimumab recipients. Serious infections such as tuberculosis, sepsis, and opportunistic infections may occur. In clinical trials, sepsis, influenza, pneumonia, cellulitis, abscess, pulmonary and extra-pulmonary tuberculosis, invasive fungal infections, and hepatitis B infection were noted. Other infections reported during clinical trials included septic shock (less than 1%), atypical mycobacterial infection (less than 1%), pyelonephritis (less than 1%), bacterial arthritis (less than 1%), and infective bursitis (less than 1%), pneumonia (less than 1%), abscess (less than 1%), and superficial fungal infection (less than 1%). Serious infections occurred in 0.9% to 1.4% of golimumab recipients and in 0% to 1.3% of control-treated patients across phase 3, 16- and 24-week trials in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis patients; the incidence of serious infection was similar between golimumab and placebo patients with ulcerative colitis. The incidence of active tuberculosis ranged from 0.23 to 0.52 per 100 patient-years for golimumab recipients as compared with 0 per 100 patient-years for placebo recipients in some trials. Testing for latent tuberculosis is needed before and during golimumab initiation. Start treatment for tuberculosis for a positive test result for latent tuberculosis. An induration of at least 5 mm with tuberculin skin testing is considered a positive result even for patients previously vaccinated with BCG. Monitor all patients regardless of latent TB test result for active TB. Patients taking TNF blockers are at increased risk of serious infections including invasive fungal infections such as histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis, candidiasis, cryptococcosis, as well as other opportunistic infections. Histoplasmosis and other invasive fungal infections are not consistently recognized in patients taking TNF blockers, which has resulted in delayed appropriate treatment that sometimes led to death. Consider empiric antifungal treatment for patients who develop a systemic illness and reside or travel to regions where mycoses are endemic. A complete diagnostic workup that may include fungal cultures, histopathological or cytological evaluations, antigen detection, and serum antibody titers is advised. Signs and symptoms of possible systemic fungal infection include pyrexia, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, or other serious systemic illness with or without concomitant shock. If possible, consultation with an infectious disease specialist should be sought. Closely follow patients who develop an infection while taking golimumab; drug discontinuation is recommended in patients who develop a serious infection, as fatalities have resulted in some cases. The decision to restart the TNF blocker should include a reevaluation of the benefits and risks of TNF blockers, especially in patients who live in regions of endemic mycoses.
Golimumab may be associated with a risk for new primary malignancy. Malignancies of various types have been reported in clinical trials. Lymphomas, including Hodgkin's and non-Hodgkin's lymphoma, account for approximately half the reported malignancy cases. Other cancers included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months of therapy (range, 1 to 84 months), and most patients were receiving concomitant immunosuppressants. In clinical trials, 6 of 309 golimumab 50, 100, or 200 mg recipients developed malignancies other than nonmelanoma skin cancers as compared with none of the control group. In this study, 3 of the 6 patients who developed cancer received a 200 mg dose. Malignancies, some fatal, have been reported among children, adolescents, and young adults who started treatment with TNF-blocking agents at 18 years of age or younger. Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), a cancer with a very aggressive disease course that is usually fatal, have been reported in patients treated with TNF blockers. Most cases occurred in adolescent and young adult males with Crohn's disease or ulcerative colitis. Almost all these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or before diagnosis; carefully consider the potential risk of golimumab receipt with the combination of azathioprine or 6-mercaptopurine. There were no cases of lymphoma through week 60 of golimumab ulcerative colitis studies. In trials of adults with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, the incidence of lymphoma per 100 patient-years of follow-up was 0.21 (95% CI 0.03, 0.77) among golimumab recipients as compared with 0 (95% CI 0, 0.96) among placebo recipients. The incidence of lymphoma among golimumab recipients was 3.8-fold higher than expected in the general US population, but patients with chronic inflammatory diseases, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at several fold higher risk for lymphoma and leukemia development than the general population even in the absence of TNF-blocking therapy. Acute and chronic leukemia have been reported with TNF blocker use, including golimumab, in patients with rheumatoid arthritis and other indications. Even in the absence of TNF-blocker therapy, patients with rheumatoid arthritis may be at an approximately 2-fold higher risk of developing leukemia than the general population. In a trial of 1-year duration, no cases of lymphoma were noted among golimumab recipients for ulcerative colitis. The incidence of malignancies other than lymphoma in golimumab-treated patients was similar to that expected in the general US population. In a controlled trial evaluating the IV formulation of golimumab in patients with rheumatoid arthritis, 1 case of malignancy other than lymphoma or nonmelanoma skin cancer occurred over 24 weeks among golimumab treated patients (n = 463) who received the drug in combination with methotrexate. The incidence of malignancies other than lymphoma and nonmelanoma skin cancers per 100 patient-years of follow-up was 0.56 (95% CI 0.01, 3.11) among intravenous golimumab recipients with rheumatoid arthritis compared to 0 (95% CI 0, 3.79) in the placebo group. Cases of acute and chronic leukemia, melanoma, and Merkel cell carcinoma have been reported post-marketing with the TNF blockers, including golimumab. Before prescribing golimumab, especially in adolescents and young adults, carefully weigh the risks and benefits of using golimumab due to the potential increased risk for cancers including HSTCL. Educate patients and caregivers about the signs and symptoms of malignancies such as HSTCL, so that they are aware of and can seek evaluation and treatment of any signs or symptoms such as splenomegaly, hepatomegaly, abdominal pain, persistent pyrexia, night sweats, and weight loss. Monitor for the emergence of malignancies when a patient has been treated with golimumab. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Regular screening for dysplasia is recommended for all patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma. If a malignancy develops, consider the risks and benefits of continued golimumab receipt.
An injection site reaction such as erythema, itching, or burning may occur with subcutaneous administration. In rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis clinical trials, 6% of golimumab recipients had an injection site reaction (injection site erythema, hives, induration, pain, bruising, local itching, irritation, and/or paresthesia) and at incidences higher than with placebo. Most reactions were mild and consisted of injection site erythema. In a 6-week ulcerative colitis trial, 3.4% of golimumab patients and 1.5% of placebo patients experienced injection site reactions, which were mainly erythema.
A possible association exists between the development of psoriasis and the use of a TNF blocker such as golimumab. During clinical trial evaluation of golimumab, new onset or worsening psoriasis, palmar/plantar psoriasis, and pustular psoriasis occurred in less than 1% of patients. In addition, the FDA reviewed 69 cases of new onset psoriasis including 17 cases of pustular psoriasis and 15 cases of palmoplantar psoriasis in patients using TNF blockers for the treatment of autoimmune and rheumatic conditions other than psoriasis and psoriatic arthritis. The development of psoriasis during TNF blocker receipt occurred from weeks to years after drug initiation. Most patients had psoriasis improvement after TNF blocker discontinuation. None of the patients reported pre-existing psoriasis before TNF blocker initiation. Exacerbation of existing psoriasis has also been noted with other TNF blockers; TNF-blocker discontinuation led to psoriasis improvement in most patients. Psoriasis recurrence upon rechallenge with a different TNF-blocker has been noted among some patients. Monitor patients for the emergence of or worsening of psoriasis during TNF blocker receipt. Consider golimumab discontinuation for severe cases and for cases that do not improve or that worsen despite topical treatments.
In clinical trials, hypertension occurred in 3% of 1,659 patients who received golimumab and in 2% of 639 patients who received placebo; hypertension occurred in 3% of 463 patients who received golimumab in combination with methotrexate. Dizziness was noted in 2% of subcutaneous golimumab recipients; dizziness occurred in less than 1% of intravenous golimumab recipients during clinical trials.
Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF antagonists, including golimumab. During clinical trials of other TNF antagonists in the treatment of CHF, there was an increase in mortality and more CHF exacerbations requiring hospitalizations in patients receiving a TNF antagonist than patients not receiving a TNF antagonist. Golimumab has not been formally studied in patients with heart failure. If golimumab is administered to patients with heart failure, monitor closely for signs or symptoms of worsening disease. Golimumab cessation is recommended if new or worsening heart failure symptoms develop.
Antibody formation, based on the enzyme immunoassay (EIA method) against golimumab during 6 months of drug receipt, occurred in 4% of patients in Phase 3 rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis trials. Patients who received golimumab with methotrexate had a lower rate of antibody development (2%) than patients who did not receive methotrexate (7%). Based on the drug-tolerant EIA method, antibodies were detected in 16%, 28%, and 24% of patients in the Phase 3 rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis trials, respectively. In these trials, patients who received golimumab with methotrexate had a lower incidence of antibody formation compared to without methotrexate; 7% vs. 35%, respectively, in rheumatoid arthritis, 18% vs. 38%, respectively in psoriatic arthritis, and 6% vs. 29%, respectively, in ankylosing spondylitis trials. In ulcerative colitis trials, 3%, 28%, and 69% of golimumab patients were positive, negative, or inconclusive for antibodies, respectively. Patients who received golimumab with immunomodulators (methotrexate, azathioprine, or 6-mercaptopurine) had a lower rate of antibody development (2%) than patients who did not receive immunomodulators (4%). Most patients found to have a positive antibody response in Phase 2 and 3 trials were determined to have neutralizing antibodies. Based on the drug-tolerant EIA method, 21% of golimumab patients in ulcerative colitis trials tested positive for antibodies compared to 79% of patients who tested negative. Ulcerative colitis patients who received golimumab with immunomodulators had a lower incidence of antibody formation compared to those who did not receive immunomodulator therapy, 12% and 26%, respectively. A trend of decreasing drug concentrations with increasing antibody titers was observed in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis; however, a trend towards decreased efficacy was only observed with ulcerative colitis. Antibody formation to the IV formulation of golimumab occurred in 3% of rheumatoid arthritis patients who received the drug in combination with methotrexate; all were neutralizing antibodies. Based on the drug-tolerant EIA method, 21%, 19%, 19%, and 31% of patients developed antibodies to golimumab in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis trials, respectively. Patients with golimumab antibodies were generally found to have lower trough steady-state concentrations. In addition to antibody formation against golimumab, use of TNF-blockers has been associated with the formation of autoantibodies and with the development of lupus-like symptoms or a lupus-like syndrome. In clinical trials through week 14, no association was found between golimumab treatment and newly positive anti-dsDNA antibodies, and it remained uncommon at 1 year. However, 4% of golimumab patients compared to 2.6% of control patients were newly antinuclear antibody (ANA)-positive at 1 year in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis trials. In ulcerative colitis trials, the incidence of patients who became ANA-positive was the same for patients that received golimumab induction plus maintenance therapy and golimumab induction plus placebo therapy. At 1 year, 0.5% of ulcerative colitis patients who received golimumab induction plus maintenance therapy developed anti-dsDNA antibodies compared to 0% of patients who received golimumab induction plus placebo maintenance. At 20 weeks of a rheumatoid arthritis trial, 17% of IV golimumab patients and 13% of control patients were newly ANA-positive. One of the golimumab patients had newly positive anti-dsDNA antibodies. If a patient develops a lupus-like syndrome after treatment with golimumab, treatment should be discontinued.
Use of TNF blockers, of which golimumab is a member, has been associated with rare cases of new onset or exacerbation of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS) and peripheral demyelinating disorders, including Guillain-Barre syndrome. Cases of central demyelination, MS, optic neuritis, and peripheral demyelinating polyneuropathy have rarely been reported in patients treated with golimumab. In clinical trials of golimumab, cases of central demyelination, multiple sclerosis, and peripheral demyelinating polyneuropathy have been reported in less than 1% of patients. Pooled data from phase 3 trials comparing golimumab +/- Disease Modifying Antirheumatic Drugs (DMARD) to placebo +/- DMARD in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis indicated that paresthesias were reported more frequently in patients in the golimumab/DMARD group (2%) than the placebo/DMARD group (1%). There was one case of CNS demyelination in a patient who received golimumab 400/200 mg during induction, but placebo during the maintenance phase. Paresthesias were also reported in less than 1% of rheumatoid arthritis patients who received intravenous golimumab in combination with methotrexate during a 24-week clinical trial. Exercise caution when considering the use of golimumab in patients with central or peripheral nervous system demyelinating disorders. Instruct patients to immediately report any symptoms such as vision changes, weakness in the arms or legs, or symptoms of peripheral neuropathy such as numbness or tingling in any part of the body. Consider golimumab discontinuation if a central or peripheral nervous system demyelinating disorder develops.
Rare reports of pancytopenia including aplastic anemia have occurred with TNF-blockers. There have been reports of pancytopenia, thrombocytopenia, neutropenia, aplastic anemia, leukopenia, and agranulocytosis in patients receiving golimumab. Leukopenia and neutropenia occurred in 1% and less than 1% of rheumatoid arthritis patients who received intravenous golimumab in combination with methotrexate during a 24 week clinical trial, respectively. Patients who develop possible signs and symptoms of blood dyscrasias should be instructed to seek immediate medical attention. Use caution when using golimumab in patients who have or have had confirmed significant cytopenias.
Pooled data from phase 3 trials comparing golimumab +/- Disease Modifying Antirheumatic Drugs (DMARD) to placebo +/- DMARD in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis indicated that constipation was reported more frequently in patients in the golimumab/DMARD group (1%) than the placebo/DMARD group (less than 1%). Constipation occurred in less than 1% of patients treated with intravenous golimumab in combination with methotrexate during clinical trials.
During clinical trial evaluation of golimumab, cutaneous vasculitis and systemic vasculitis were reported in less than 1% of golimumab-treated patients.
Fever was reported in 2% of 463 patients with rheumatoid arthritis treated with intravenous golimumab in combination with methotrexate during a 24 week placebo controlled trial. Among patients treated with placebo and methotrexate, the incidence of fever was 1%.
Rash (unspecified) has occurred in 3% of patients who received IV golimumab. Skin exfoliation (exfoliative dermatitis), lichenoid reactions (lichen planus-like eruption), rash, and bullous rash have been observed postmarketing with golimumab. Anaphylactoid reactions, other serious hypersensitivity reactions or anaphylaxis may occur; cases of these events have been reported with postmarketing use of both IV and subcutaneous golimumab. Hypersensitivity reactions including urticaria, pruritus, dyspnea, hives, and nausea have been reported; some reactions occurred after the first administration of golimumab and with IV use, many of these reactions occur within an hour of receiving a golimumab IV infusion. Infusion-related reactions occurred in 1.1% of patients who received IV golimumab in combination with methotrexate; rash was the most common type of event and serious infusion-related reactions have not been reported. If a serious allergic reaction occurs, immediately discontinue golimumab therapy and institute appropriate medical therapy. Other immune system reactions reported postmarketing have included sarcoidosis. Serious respiratory disorders have included interstitial lung disease.
The use of TNF blockers, including golimumab, has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic hepatitis B carriers (i.e., surface antigen positive). In some instances, hepatitis B exacerbation/reactivation occurring in conjunction with TNF blocker therapy has been fatal. The majority of these reports have occurred in patients who received concomitant immunosuppressants. All patients should be tested for HBV status before initiating TNF-blocker therapy. For patients who test positive for hepatitis B surface antigen, consultation with a physician with expertise in the treatment of hepatitis B is recommended before initiating TNF-blocker therapy. In patients who develop HBV reactivation, TNF blockers should be stopped and antiviral therapy with appropriate supportive treatment should be initiated. The safety of resuming TNF-blockers after HBV reactivation has been controlled is not known.
Patients who receive golimumab or other TNF blockers are at increased risk for developing serious infections that may result in hospitalization and/or death. Patients with a history of recurrent infections with underlying conditions that may predispose them to infections (e.g., elderly and patients with advanced or uncontrolled diabetes mellitus, malignancy, bone marrow suppression, or immunosuppression) may not be appropriate candidates for treatment. Evaluate the risks and benefits before beginning golimumab therapy in patients with chronic or recurrent infections or in patients with underlying conditions predisposing them to infection. Do not administer golimumab to patients with a clinically important active infection like sepsis or influenza as host defenses will be affected. Most serious infections have occurred in patients receiving concurrent immunosuppressives such as methotrexate and corticosteroid therapy. Serious infections may involve multiple organ systems and include bacterial infection (Legionella and Listeria), mycobacterial infection (disseminated tuberculosis or extrapulmonary tuberculosis), fungal infection (histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, listeriosis, Pneumocystis jiroveci pneumonia), parasitic infection, viral infection, and other opportunistic infections. Patients with invasive fungal infections (specifically histoplasmosis) may present with disseminated rather than localized disease. Health care providers should be aware that antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Carefully consider the risks before initiating therapy in patients who reside in histoplasmosis, blastomycosis, or coccidioidomycosis endemic zones. In patients who develop severe systemic illness, consider administering empiric antifungal therapy. Patients need to be evaluated for tuberculosis risk factors and for latent or active tuberculosis infection with a tuberculin skin test both before and during treatment. The possibility of anergy needs to be considered when interpreting the test result. If tuberculin skin testing is performed for latent tuberculosis infection, an induration size of 5 mm or greater should be considered positive even if the patient was vaccinated previously with Bacille Calmette-Guerin. Cases of tuberculosis have occurred and treatment of latent infection should be started before golimumab initiation. Treatment of latent tuberculosis in patients with a reactive tuberculin test reduces the risk of tuberculosis reactivation. Consider antituberculosis therapy before golimumab initiation in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed and in patients who have several or highly significant risk factors for tuberculosis infection (e.g., close contact with infected persons or travel to endemic zones) and have a negative test for latent tuberculosis. Monitor all patients for signs and symptoms of tuberculosis including those who tested negative for latent tuberculosis infection prior to initiating golimumab, patients who are on treatment for latent tuberculosis, or patients who were previously treated for tuberculosis infection. Educate patients about the symptoms of infection, and closely monitor patients for signs and symptoms of an infection during and after treatment. Patients who develop a new infection during treatment should be closely monitored and evaluated for appropriate antimicrobial therapy. If a patient develops a serious infection or sepsis, discontinue golimumab. In addition, care should be taken when switching from one biologic product to another as overlapping biological activity may further increase the risk of infection. Health care providers are encouraged to report adverse events to the MedWatch Safety Information and Adverse Event Reporting Program by telephoning 1-800-332-1088 or by completing the form online.
Golimumab neutralizes the biological activity of TNF-alpha; therefore, golimumab may affect host defenses against neoplastic disease. Cases of new primary malignancy, some fatal, have been reported among children, adolescents, and young adults (initiation of therapy at 18 years of age or younger), who received treatment with drugs in the TNF-blocker class, of which golimumab is a member. Approximately 50% of these malignancy cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression, and malignancies that are not usually observed in pediatric patients. Leukemia, melanoma, and Merkel cell carcinoma have been reported in patients treated with TNF-blocking agents, including golimumab. Most malignancies occurred after a median of 30 months (range 1 to 84 months) after the first dose of TNF-blocker therapy. Most of the patients were receiving concomitant immunosuppressants. These cases were reported postmarketing and are derived from a variety of sources, including registries and spontaneous postmarketing reports. Also, a greater portion of malignancies occurred in the TNF-blocker group as compared with the control group among patients at higher risk for malignancies such as patients with chronic obstructive pulmonary disease (COPD) or patients with Wegener's granulomatosis treated with concomitant cyclophosphamide. Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma that has a very aggressive disease course and is usually fatal, have been reported mostly in adolescent and young adult males with inflammatory bowel disease such as Crohn's disease or ulcerative colitis treated with TNF-blockers; almost all cases have occurred in patients who had received a TNF-blocker concomitantly with either azathioprine or 6-mercaptopurine (6-MP) at or before diagnosis. However, whether or not the occurrence of hepatosplenic T-cell lymphoma is related to a TNF blocker or to a TNF blocker in combination with these other immunosuppressants is unknown. As a risk for the development for hepatosplenic T-cell lymphoma cannot be excluded, carefully consider the potential risk of golimumab with either azathioprine or 6-MP. Screen all patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma such as those with long-standing ulcerative colitis or primary sclerosing cholangitis and those with a history of dysplasia or colon carcinoma for dysplasia at regular intervals before and during golimumab receipt. Screening includes colonoscopy and biopsies per local recommendations. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Consider the risks and benefits of golimumab before treatment initiation in patients with a known malignancy other than a successfully treated non-melanoma skin cancer. Consider also the risks and benefits of golimumab continuation in patients who develop a malignancy including newly diagnosed dysplasia. Use of golimumab by patients with malignancy risk factors, a malignancy history, or current malignancy may be unadvisable.
Golimumab should be used with caution in patients with heart failure. Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with golimumab and other TNF-blockers. Infliximab, a similar therapeutic agent to golimumab, is contraindicated in patients with moderate to severe heart failure (NYHA Class III/IV). Increased mortality and worsening heart failure were noted in a study of infliximab-treated patients. Although golimumab has not been studied in patients with a history of CHF, worsening heart failure may develop. If golimumab is initiated, closely monitor patients. Golimumab cessation is recommended if new or worsening heart failure symptoms develop.
Use of TNF blockers, of which golimumab is a member, has been associated with rare cases of new onset or exacerbation of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS) and peripheral demyelinating disorders, including Guillain-Barre syndrome. Cases of central demyelination, MS, optic neuritis, and peripheral demyelinating polyneuropathy have rarely been reported in patients treated with golimumab. Use caution in considering the use of TNF blockers, including golimumab, in patients with central or peripheral nervous system demyelinating disorders. Discontinuation of golimumab should be considered if these disorders develop.
There have been postmarketing reports of pancytopenia, leukopenia, neutropenia, aplastic anemia, thrombocytopenia, and agranulocytosis (severe neutropenia) in patients receiving TNF blockers, including in golimumab-treated patients. Caution should be exercised when using TNF blockers, including golimumab, in patients who have or have had significant cytopenias.
Treatment with golimumab may result in the formation of autoantibodies and in the development of a syndrome suggestive of autoimmune disease or lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment, golimumab treatment should be discontinued. Have patients report if they get any chest discomfort or pain that does not go away, shortness of breath, joint pain, or a typical rash on the cheeks or arms that gets worse in the sun.
The needle cover on the golimumab prefilled syringe as well as the prefilled syringe in the prefilled SmartJect autoinjector for subcutaneous use contains dry natural rubber (a derivative of latex). Instruct patients with rubber or latex hypersensitivity not to handle the needle cover on the prefilled syringe or the needle cover of the prefilled syringe within the autoinjector cap.
There are no adequate and well-controlled trials of golimumab in pregnant women; use during pregnancy should be balanced with the risks and benefits of continuing therapy for the individual patient versus the risks posed by uncontrolled disease or disease flares. Experts and guidelines recommend that golimumab may be continued during pregnancy, as cohort and registry monitoring data for TNF-blocker therapy during pregnancy have not revealed an increase in adverse fetal outcomes. Golimumab is transported across the placenta and may affect immune response in the in utero exposed infant. To minimize drug transfer at birth, it is recommended to administer the final golimumab dose 4 to 6 weeks prior to anticipated delivery, then resume the drug postpartum. Neonates and infants born to women treated with TNF-blockers during their pregnancy may be at increased risk of infection for up to 6 months, and administration of live vaccines to infants exposed to golimumab in utero is not recommended for 6 months after the mother's last injection during pregnancy. In embryo-fetal toxicology studies involving pregnant cynomolgus monkeys with doses that produced golimumab exposures approximately 360 times greater than the maximum recommended human dose (MRHD) for subcutaneous administration and 200 times the MRHD for intravenous administration, no evidence of maternal or fetal harm was noted.
Avoid live vaccination in patients treated with golimumab. Whenever possible, update immunizations prior to treatment initiation, following current immunization guidelines for patients receiving immunosuppressive agents. Administration of live vaccines to infants exposed to golimumab in utero is not recommended for 6 months after the mother's last golimumab infusion during pregnancy. Limited data are available on the response to live vaccination, or on the secondary transmission of infection by live vaccines. Use of live vaccines could result in clinical infections, including disseminated infections. In addition, therapeutic infectious agents (e.g., BCG bladder instillation) could result in clinical infections and should not be administered concurrently with golimumab.
There is no information regarding the presence of golimumab in human milk, the effects on breastfed infants, or the effects on milk production. Experts and guidelines consider golimumab and other biologic use to be compatible during breast-feeding; consider the mother's clinical need for golimumab and the benefits of breast-feeding and any potential adverse drug effects on the infant. Adalimumab and infliximab may be potential alternatives to consider during breast-feeding. However, indication and patient-specific factors should be assessed before choosing an alternative agent. Maternal IgG is known to be present in human milk. In the pre- and postnatal development study in cynomolgus monkeys in which golimumab was administered subcutaneously during pregnancy and lactation, golimumab was detected in the breast milk at concentrations that were approximately 400-fold lower than the maternal serum concentrations. If golimumab is transferred to human milk, the effects on local exposure in the gastrointestinal tract and the potential for limited systemic exposure to the infant are unknown. In a study involving infants breast-fed by women with inflammatory bowel disease who were receiving biologic therapies, low concentrations of adalimumab and infliximab were detected in breast milk samples. Golimumab was not detected in the breast milk of the one woman enrolled in the study was receiving this mediccation. Infection risk and rates of milestone achievements were similar between breast-fed infants of women on biologics, immunomodulators, or combination therapies compared to infants not exposed to these medications or non-breast-fed infants.
Because there is a higher incidence of infections in the geriatric population in general, use caution in treating geriatric patients with golimumab. In clinical trials for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, no overall difference was noted in the adverse reactions, serious infections, or serious adverse events of subcutaneous golimumab between geriatric and younger adult patients. There were insufficient numbers of geriatric patients in golimumab trials for subcutaneous use in ulcerative colitis and intravenous use in rheumatoid arthritis to determine whether they respond differently from younger patients.
For the treatment of moderately to severely active rheumatoid arthritis in combination with methotrexate:
Subcutaneous dosage (Simponi only):
Adults: 50 mg subcutaneously once monthly. Corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or nonbiologic disease modifying antirheumatic drugs (DMARDs) may be continued during subcutaneous golimumab therapy. Subcutaneous golimumab has been evaluated in adult patients with moderately to severely active rheumatoid arthritis (RA) in 3 multicenter, randomized, double-blind, controlled trials (n = 1,542). In patients with active RA previously treated with 1 or more doses of a tumor necrosis factor (TNF)-blocker, a 20% improvement in the American College of Rheumatology (ACR20) score at week 14 (primary endpoint) was achieved in 40% of patients who received subcutaneous golimumab 50 mg plus methotrexate compared with 17% of patients who received placebo plus methotrexate. In patients with active RA despite a stable dose of at least 15 mg/week of methotrexate and who had not been previously treated with a biologic TNF-blocker, a 20% improvement in the ACR20 score at week 14 (primary endpoint) was reported in 55% of patients who received subcutaneous golimumab 50 mg plus methotrexate compared with 33% of patients who received methotrexate alone in another trial. In patients with active RA who had not previously received methotrexate or a biologic TNF-blocker, a 50% improvement in the American College of Rheumatology (ACR50) score at week 24 (primary endpoint) occurred in 40% of patients who received subcutaneous golimumab 50 mg plus methotrexate (up to 20 mg/week) compared with 29% of patients who received methotrexate alone in a third trial. Clinical practice guidelines recommend a TNF blocker +/- methotrexate as an option for patients with a disease duration of less than 6 months and high disease activity with poor prognostic feature presence. For established disease, adding or switching to an anti-TNF biologic is an option for patients with moderate or high disease activity after 3 months of methotrexate monotherapy or DMARD combination therapy. A switch to a different anti-TNF biologic is an option for patients with moderate or high disease activity after 3 months or more of a TNF blocker or with a non-serious adverse event. Also, a switch to an anti-TNF biologic is an option for patients with moderate or high disease activity after 6 months or more of a non-TNF biologic or with a serious or non-serious adverse event to the drug. The goal is low disease activity or remission.
Intravenous dosage (Simponi Aria only):
Adults: 2 mg/kg/dose IV every 4 weeks for 2 doses, then 2 mg/kg/dose IV every 8 weeks. Corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), non-biologic disease modifying antirheumatic drugs (DMARDs), and/or analgesics may be continued during IV golimumab therapy. In patients with active rheumatoid arthritis despite 3 months or more of methotrexate therapy, a 20% improvement in the American College of Rheumatology (ACR20) score at week 14 (primary endpoint) was achieved in 58.5% of patients who received IV golimumab plus methotrexate compared with 24.9% of patients who received placebo plus methotrexate (p less than 0.001, GO-FURTHER trial). Patients were permitted to receive standard prophylaxis for infusion reactions (e.g., acetaminophen, antihistamines) but not corticosteroids. A significant difference in ACR20 response was observed by week 2. Additionally, a good or moderate European League Against Rheumatism (EULAR) response was achieved at week 14 in significantly more patients who received IV golimumab compared with placebo (81.3% vs. 40.1%; p less than 0.001). In this same trial, patients receiving golimumab plus methotrexate demonstrated greater improvement from baseline compared to placebo plus methotrexate in the physical component summary, mental component summary scores, and in all 8 domains of the Short Form Health Survey (SF-36).
For the treatment of active ankylosing spondylitis (AS):
Subcutaneous dosage (Simponi only):
Adults: 50 mg subcutaneously once per month. May be used alone or in combination with methotrexate or other non-biologic DMARDs. Corticosteroids, NSAIDs, and/or analgesics may be continued during golimumab receipt.
Intravenous dosage (Simponi Aria only):
Adults: 2 mg/kg IV over 30 minutes. Repeat this dose 4 weeks later and then administer every 8 weeks thereafter.
For the treatment of active psoriatic arthritis (PsA):
Subcutaneous dosage (Simponi only):
Adults: 50 mg subcutaneously once per month. May be used alone or in combination with methotrexate or other non-biologic DMARDs. Corticosteroids, NSAIDs, and/or analgesics may be continued during golimumab receipt. In a study in patients with psoriatic arthritis, 51% of 146 recipients of golimumab 50 mg subcutaneously every 4 weeks had an ACR20 at week 14 as compared with 9% of 113 placebo recipients, and 40% of golimumab recipients had at least a 75% improvement in the Psoriasis Area and Severity Index (PASI) criteria as compared with 2.5% of placebo recipients. Further, a median 25% improvement in the Nail Psoriasis Severity Index score was noted for golimumab recipients; no change was noted for placebo recipients.
Intravenous dosage (Simponi Aria only):
Adults: 2 mg/kg/dose IV at weeks 0 and 4, then every 8 weeks thereafter.
Children and Adolescents 2 to 17 years: 80 mg/m2/dose IV at weeks 0 and 4, then every 8 weeks thereafter.
For the treatment of active polyarticular juvenile idiopathic arthritis (pJIA):
Intravenous dosage (Simponi Aria only):
Children and Adolescents 2 to 17 years: 80 mg/m2/dose IV at weeks 0 and 4, then every 8 weeks thereafter.
For the treatment of moderately to severely active ulcerative colitis, in persons who have corticosteroid dependence or an inadequate response or intolerance to oral aminosalicylates, corticosteroids, or thiopurines:
Subcutaneous dosage (Simponi only):
Adults: 200 mg subcutaneously at week 0, then 100 mg subcutaneously at week 2, then 100 mg subcutaneously every 4 weeks. Guidelines strongly recommend golimumab for induction of remission in persons with moderately to severely active ulcerative colitis and for maintenance of remission in persons who respond to golimumab induction.
Therapeutic Drug Monitoring:
Target concentrations of golimumab in patients with Inflammatory Bowel Disease per guidelines
-Week 6: at least 3 to 7 mcg/mL
-Maintenance therapy: at least 1 to 3 mcg/mL
Maximum Dosage Limits:
-Adults
50 mg/dose subcutaneously for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis; 2 mg/kg/dose IV for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis; 200 mg/dose subcutaneously for ulcerative colitis induction and 100 mg/dose subcutaneously for ulcerative colitis maintenance.
-Geriatric
50 mg/dose subcutaneously for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis; 2 mg/kg/dose IV for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis; 200 mg/dose subcutaneously for ulcerative colitis induction and 100 mg/dose subcutaneously for ulcerative colitis maintenance.
-Adolescents
80 mg/m2/dose IV for polyarticular juvenile idiopathic arthritis and psoriatic arthritis.
-Children
2 to 12 years: 80 mg/m2/dose IV for polyarticular juvenile idiopathic arthritis and psoriatic arthritis.
1 year: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Abatacept: (Major) Concomitant use of abatacept with other biologic agents, such as tumor necrosis factor (TNF) inhibitors, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. In controlled clinical trials, patients receiving concomitant abatacept and TNF inhibitor therapy experienced more infections (63%) and serious infections (4.4%) as compared with patients treated with only TNF inhibitors (43% and 0.8%, respectively). These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of abatacept with a TNF inhibitor. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept therapy.
Adalimumab: (Contraindicated) Do not use golimumab in combination with other tumor necrosis factor (TNF) modifier therapy, including adalimumab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if golimumab is used concomitantly with adalimumab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Anakinra: (Major) Avoid the concomitant use of anakinra with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection with no additional clinical benefit. Data suggest a higher rate of serious infections when anakinra and a TNF inhibitor is used in combination with anakinra compared with either drug given alone. Neutropenia (1,000/mcL or less) was observed in 2% of patients receiving the combination. The use of anakinra with a TNF inhibitor in combination did not yield any additional clinical benefit as compared to the use of the TNF inhibitor alone.
Anifrolumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Antithymocyte Globulin: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Azathioprine: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Baricitinib: (Major) Concomitant use of baricitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Basiliximab: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Belimumab: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Therefore, belimumab use is not recommended in combination with TNF blockers. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Canakinumab: (Major) Avoid concomitant administration of canakinumab with tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. An increased incidence of serious infections and an increased risk of neutropenia have been associated with administration of another IL-1 blocker in combination with TNF inhibitors. Based upon the potential for similar interactions, concomitant administration of canakinumab and TNF inhibitors is not recommended.
Certolizumab pegol: (Contraindicated) Do not use certolizumab in combination with other tumor necrosis factor (TNF) modifier therapy, including golimumab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if certolizumab is used concomitantly with golimumab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Chikungunya Vaccine, Live: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cyclosporine: (Moderate) If golimumab is initiated or discontinued in a patient taking cyclosporine, monitor the cyclosporine concentration; cyclosporine dose adjustment may be needed. Monitor closely for additive immunosuppression and for infection. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection. The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha) during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during golimumab receipt. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as cyclosporine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Etanercept: (Contraindicated) Do not use golimumab in combination with other tumor necrosis factor (TNF) modifier therapy, including etanercept, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if golimumab is used concomitantly with etanercept. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Infliximab: (Contraindicated) Do not use golimumab in combination with other tumor necrosis factor (TNF) modifier therapy, including infliximab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if golimumab is used concomitantly with infliximab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Intranasal Influenza Vaccine: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Live Vaccines: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Methotrexate: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Methylprednisolone: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Natalizumab: (Major) Natalizumab for Crohn's disease should not be used in combination with tumor necrosis factor (TNF) modifiers. Coadministration may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy and other opportunistic infections. Ordinarily, patients with mulitple sclerosis who are receiving chronic TNF-modifier therapy should not be treated with natalizumab.
Prednisolone: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Prednisone: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
Rilonacept: (Contraindicated) Concurrent use of rilonacept and tumor necrosis factor (TNF) modifiers is not advised, as the risk of serious infections may be increased. Although concurrent use has not been evaluated in clinical trials, an increased incidence of serious infections and neutropenia has been associated with administration of another drug that blocks IL-1 in combination with TNF inhibitors.
Rituximab: (Major) Avoid the concomitant use of rituximab with golimumab, a tumor necrosis factor (TNF) inhibitor; coadministration may result in additive immunosuppression and an increased risk of infection. Higher rates of serious infection were observed in patients with rheumatoid arthritis treated with rituximab who received subsequent treatment with a TNF inhibitor.
Rituximab; Hyaluronidase: (Major) Avoid the concomitant use of rituximab with golimumab, a tumor necrosis factor (TNF) inhibitor; coadministration may result in additive immunosuppression and an increased risk of infection. Higher rates of serious infection were observed in patients with rheumatoid arthritis treated with rituximab who received subsequent treatment with a TNF inhibitor.
Rotavirus Vaccine: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Sarilumab: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Theophylline, Aminophylline: (Moderate) If golimumab is initiated or discontinued in a patient taking aminophylline, monitor the theophylline concentration; aminophylline dose adjustment may be needed. The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha) during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during golimumab receipt. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as aminophylline. (Moderate) If golimumab is initiated or discontinued in a patient taking theophylline, monitor the theophylline concentration; theophylline dose adjustment may be needed. The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha) during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during golimumab receipt. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as theophylline.
Tocilizumab: (Major) Avoid the concomitant use of tocilizumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Tofacitinib: (Major) Concomitant use of tofacitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Tofacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Typhoid Vaccine: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Upadacitinib: (Major) Concomitant use of upadacitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of increased immunosuppression and increased infection risk. Upadacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Vedolizumab: (Major) Vedolizumab should not be used in combination with tumor necrosis factor (TNF) modifiers because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections. Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with vedolizumab.
Warfarin: (Moderate) If golimumab is initiated or discontinued in a patient taking warfarin, monitor the INR; warfarin dose adjustment may be needed. The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha) during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during golimumab receipt. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as warfarin, and alter the clinical response to warfarin treatment.
Yellow Fever Vaccine, Live: (Contraindicated) Do not administer live vaccines to golimumab recipients. Limited data are available on the response to live vaccination or on the risk of infection or infection transmission after the administration. Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Golimumab neutralizes the biological activity of tumor necrosis factor (TNF)-alpha by binding to it and blocking its interaction with cell surface TNF receptors. Golimumab binds to both the soluble and the transmembrane bioactive forms of human TNF-alpha. Golimumab does not bind to or inactivate lymphotoxin (TNF-beta), which is a related cytokine that utilizes the same receptors as TNF-alpha. Elevated TNF-alpha concentrations in the blood, synovium, and joints have been implicated in the pathophysiology of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Tumor necrosis factor-alpha is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Biological activities attributed to TNF-alpha include induction of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, G-CSF, and GM-CSF; enhancement of leukocyte migration by increasing endothelial layer permeability; expression of adhesion molecules responsible for leukocyte infiltration such as E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) by endothelial cells and leukocytes; activation of neutrophil and eosinophil functional activity; proliferation of fibroblasts; inhibition of osteoblast differentiation; upregulation of Fas-mediated apoptosis of osteoblasts; synthesis of prostaglandins; indirect induction of osteoclast differentiation and bone resorption; and induction of acute phase and other liver proteins. Activated macrophages release TNF-alpha, which acts on chondrocytes, fibroblasts, and osteoclasts to release metalloproteinases (MMP) and other effector molecules that induce the migration of polymorphonuclear cells.
Golimumab receipt to adults with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis was associated with reductions in C-reactive protein, IL-6, matrix MMP-3, ICAM-1, and vascular endothelial growth factor concentrations.
Golimumab is administered subcutaneously or intravenously. The mean Vd is 115 mL/kg in healthy subjects and 151 mL/kg in patients with rheumatoid arthritis (RA), indicating the drug is primarily distributed in the circulatory system with limited extravascular distribution. The exact metabolic pathway of the drug is not known. The median terminal half-life of subcutaneous golimumab was estimated to be approximately 2 weeks among patients with active RA, ankylosing spondylitis, or psoriatic arthritis and the mean terminal half-life of intravenous golimumab was 14 +/- 4 days in patients with RA.
Affected cytochrome P450 isoenzymes and drug transporters: Unknown
The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines during chronic inflammation. It is expected that golimumab may normalize the formation of CYP450 enzymes during treatment. Upon initiation or discontinuation of golimumab in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.
-Route-Specific Pharmacokinetics
Intravenous Route
A mean Cmax of 44.4 +/- 11.3 mcg/mL occurred after IV administration of a 2 mg/kg dose in patients with rheumatoid arthritis. Steady-state serum concentrations were reached by week 12 when 2 mg/kg was given to patients with rheumatoid arthritis at weeks 0, 4, and every 8 weeks thereafter.
Subcutaneous Route
Steady-state concentrations were attained by week 12 with receipt of 50 mg subcutaneously every 4 weeks in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. Patients who developed anti-golimumab antibodies generally had lower steady-state serum trough concentrations. In contrast, higher mean steady-state trough concentrations were obtained among patients who also took methotrexate. Specifically, as compared to patients taking golimumab without methotrexate, the mean steady-state trough concentration was 52% higher, 36% higher, and 21% higher in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, respectively, that were taking golimumab plus methotrexate. In patients with ulcerative colitis, steady-state concentrations were attained by week 8 after receipt of 200 mg and 100 mg at week 0 and 2, followed by 100 mg every 4 weeks.
-Special Populations
Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetic parameters of golimumab has not been evaluated.
Renal Impairment
The effect of renal impairment on the pharmacokinetic parameters of golimumab has not been evaluated.
Pediatrics
Steady-state concentrations are attained by week 12 when golimumab is administered intravenously as recommended. Exposure is comparable in pediatric and adults patients. With concomitant use of methotrexate, mean steady-state trough and AUC are approximately 0.5 +/- 0.5 mcg/mL and 425 +/- 125 mcg/mL x day in patients with polyarticular juvenile idiopathic arthritis.