Patients treated with golimumab products are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions (5.1)]. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Discontinue GOMOSDI if a patient develops a serious infection.
Reported infections with TNF blockers, of which GOMOSDI is a member, include:
- Active tuberculosis, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Test patients for latent tuberculosis before GOMOSDI use and during therapy. Initiate treatment for latent TB prior to GOMOSDI use.
- Invasive fungal infections including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
- Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.
Consider the risks and benefits of treatment with GOMOSDI prior to initiating therapy in patients with chronic or recurrent infection.
Monitor patients closely for the development of signs and symptoms of infection during and after treatment with GOMOSDI, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which GOMOSDI is a member.
Patients treated with golimumab products are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death.
Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease. The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections; therefore, the concomitant use of GOMOSDI and these biologic products is not recommended.
Treatment with GOMOSDI should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants such as corticosteroids or methotrexate may be at greater risk of infection. Consider the risks and benefits of treatment prior to initiating GOMOSDI in patients:
- with chronic or recurrent infection;
- who have been exposed to tuberculosis;
- with a history of an opportunistic infection;
- who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis;
- with underlying conditions that may predispose them to infection.
Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving TNF blockers, including patients who have previously received treatment for latent or active tuberculosis. Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating GOMOSDI and periodically during therapy.
Treatment of latent tuberculosis infection prior to therapy with TNF blockers has been shown to reduce the risk of tuberculosis reactivation during therapy. Prior to initiating GOMOSDI, assess if treatment for latent tuberculosis is needed; an induration of 5 mm or greater is a positive tuberculin skin test, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG).
If patients develop a serious systemic illness and they reside or travel in regions where mycoses are endemic, consider invasive fungal infection in the differential diagnosis. Consider appropriate empiric antifungal therapy, and take into account both the risk for severe fungal infection and the risks of antifungal therapy while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. To aid in the management of such patients, consider consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections.
The use of TNF blockers including golimumab products 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, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. The majority of these reports have occurred in patients who received concomitant immunosuppressants.
Patients who are carriers of HBV and require treatment with TNF blockers should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of 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. Therefore, prescribers should exercise caution when considering resumption of TNF blockers in this situation and monitor patients closely.
Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy ≤ 18 years of age), of which GOMOSDI is a member. Approximately half the 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 children and adolescents. The 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.
In the controlled portions of clinical trials of TNF blockers, including golimumab, more cases of lymphoma have been observed among patients receiving anti-TNF treatment compared with patients in the control groups. During the controlled portions of the Phase 2 trials in RA, and the Phase 3 trials in RA, PsA and AS, the incidence of lymphoma per 100 patient-years of follow-up was 0.21 (95% CI: 0.03, 0.77) in the combined golimumab group compared with an incidence of 0 (95% CI: 0, 0.96) in the placebo group. Patients with RA and other chronic inflammatory diseases, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF-blocking therapy. Cases of acute and chronic leukemia have been reported with TNF-blocker use, including golimumab products, in rheumatoid arthritis and other indications. Even in the absence of TNF-blocker therapy, patients with rheumatoid arthritis may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.
Rare postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF-blocking agents. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. Nearly all of the reported TNF blocker associated cases have occurred in patients with Crohn's disease or ulcerative colitis. The majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine (AZA) or 6-mercaptopurine (6-MP) concomitantly with a TNF blocker at or prior to diagnosis. The potential risk with the combination of AZA or 6-MP and GOMOSDI should be carefully considered. A risk for the development for hepatosplenic T-cell lymphoma in patients treated with TNF blockers cannot be excluded.
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocking agents, including golimumab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers, including golimumab products. Some cases had a fatal outcome. In several exploratory trials of other TNF blockers in the treatment of CHF, there were greater proportions of TNF-blocker-treated patients who had CHF exacerbations requiring hospitalization or increased mortality. Golimumab products have not been studied in patients with a history of CHF and GOMOSDI should be used with caution in patients with CHF. If a decision is made to administer GOMOSDI to patients with CHF, these patients should be closely monitored during therapy, and GOMOSDI should be discontinued if new or worsening symptoms of CHF appear.
Use of TNF blockers, of which GOMOSDI 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-Barré syndrome. Cases of central demyelination, MS, optic neuritis, and peripheral demyelinating polyneuropathy have rarely been reported in patients treated with golimumab products. Exercise caution in considering the use of TNF blockers, including GOMOSDI, in patients with central or peripheral nervous system demyelinating disorders. Consider discontinuation of GOMOSDI if these disorders develop.
Autoimmunity. Treatment with TNF blockers, including GOMOSDI, may result in the formation of antinuclear antibodies (ANA) and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with GOMOSDI, treatment should be discontinued.
Use with Abatacept. In controlled trials, the concurrent administration of another TNF blocker and abatacept was associated with a greater proportion of serious infections than the use of a TNF blocker alone; and the combination therapy, compared to the use of a TNF blocker alone, has not demonstrated improved clinical benefit in the treatment of RA. Therefore, the combination of TNF blockers, including GOMOSDI, and abatacept is not recommended.
Use with Anakinra. Concurrent administration of anakinra (an interleukin-1 antagonist) and another TNF blocker was associated with a greater portion of serious infections and neutropenia and no additional benefits compared with the TNF-blocker alone. Therefore, the combination of anakinra with TNF blockers, including GOMOSDI, is not recommended.
Switching Between Biological Disease-Modifying Antirheumatic Drugs.Care should be taken when switching from one biological product to another biological product since overlapping biological activity may further increase the risk of infection.
Hematologic Cytopenias.There have been reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anemia, and thrombocytopenia in patients receiving golimumab products. Caution should be exercised when using TNF blockers, including GOMOSDI, in patients who have or have had significant cytopenias.
Live Vaccines
Patients treated with GOMOSDI may receive vaccinations, except for live vaccines. Use of live vaccines could result in clinical infections, including disseminated infections.
Therapeutic Infectious Agents
Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with GOMOSDI.
Infants born to women treated with golimumab products during their pregnancy may be at increased risk of infection for up to 6 months. Administration of live vaccines to infants exposed to GOMOSDI in utero is not recommended for 6 months following the mother’s last GOMOSDI injection during pregnancy.
Hypersensitivity Reactions.Serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported following administration of golimumab products. Some of these reactions occurred after the first administration of the golimumab products. If an anaphylactic or other serious allergic reaction occurs, administration of GOMOSDI should be discontinued immediately and appropriate therapy instituted.
The most serious adverse reactions include serious infections and malignancies.
Upper respiratory tract infection and nasopharyngitis were the most common adverse reactions reported in the combined Phase 3 RA, PsA and AS trials through Week 16, occurring in 7% and 6% of golimumab-treated patients as compared with 6% and 5% of control-treated patients, respectively.
Concomitant use of eculizumab products with plasma exchange (PE), plasmapheresis (PP) or fresh frozen plasma infusion (PE/PI) treatment can reduce serum eculizumab product concentrations and requires a supplemental dose of GOMOSDI.
Concomitant use of eculizumab products with neonatal Fc receptor (FcRn) blockers may lower systemic exposures and reduce effectiveness of eculizumab products. Closely monitor for reduced effectiveness of GOMOSDI.
GOMOSDI, in combination with methotrexate, is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis.
GOMOSDI, alone or in combination with methotrexate, is indicated for the treatment of adult patients with active psoriatic arthritis.
GOMOSDI is indicated for the treatment of adult patients with active ankylosing spondylitis.
GOMOSDI is indicated in adult patients with moderately to severely active ulcerative colitis who have demonstrated corticosteroid dependence or who have had an inadequate response to or failed to tolerate oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine for:
