Golimumabside effects

The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Infections Malignancies Congestive Heart Failure Demyelinating Disorders Hepatitis B Reactivation Autoimmunity Hematologic Cytopenias Hypersensitivity Reactions Most common adverse reactions in adults (incidence > 5%) are upper respiratory tract infection, nasopharyngitis, injection site reactions To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety data described below are based on: Five pooled, randomized, double-blind, controlled Phase 3 trials in patients with RA, PsA, and AS (Trials RA-1, RA-2, RA-3, PsA, and AS). These 5 trials included 639 control-treated patients and 1659 SIMPONI-treated patients including 1089 with RA, 292 with PsA, and 278 with AS. Three pooled, randomized, double-blind, controlled Phase 2/3 in 1233 SIMPONI-treated adult patients with UC (Trials UC-1, UC-2, and UC-3 (NCT03596645)). An open-label trial in 69 SIMPONI-treated pediatric patients weighing at least 15 kg with UC (Trial UC-3) (NCT03596645). The proportion of adult patients who discontinued treatment due to adverse reactions in the controlled Phase 3 trials through Week 16 in RA, PsA and AS was 2% for SIMPONI-treated patients and 3% for placebo-treated patients. The most common adverse reactions leading to discontinuation of SIMPONI in the controlled Phase 3 trials in RA, PsA and AS through Week 16 were sepsis (0.2%), alanine aminotransferase increased (0.2%), and aspartate aminotransferase increased (0.2%). The most common adverse drug reactions leading to discontinuation through Week 60 of the UC trials in adult patients who received SIMPONI induction and 100 mg during maintenance compared with patients who received SIMPONI induction and placebo during maintenance were tuberculosis (0.3% vs. 0.6%) and anemia (0.3% vs. 0%), respectively. Upper respiratory tract infection and nasopharyngitis were the most common adverse reactions reported in the combined Phase 3 RA, PsA and AS trials in adults through Week 16, occurring in 7% and 6% of SIMPONI-treated patients as compared with 6% and 5% of control-treated patients, respectively. Infections In adult controlled Phase 3 trials through Week 16 in RA, PsA, and AS, infections were observed in 28% of SIMPONI-treated patients compared to 25% of control-treated patients. For serious infections, see the Warnings and Precautions section. In Trial UC-1, the rates of infections were similar in SIMPONI 200/100 mg-treated patients and placebo-treated patients, or approximately 12%. Through Week 60, the incidence per patient year of infections was similar in patients who received SIMPONI induction and 100 mg during maintenance compared with patients who received SIMPONI induction and placebo during the maintenance period Trial UC-2. Demyelinating Disorders In Trial UC-1 of SIMPONI induction through Week 6, no cases of demyelination were observed in SIMPONI 200/100 mg-treated patients or placebo-treated patients. Through Week 60 in Trial UC-2, there were no cases of demyelination in the SIMPONI 100 mg group during maintenance. One case of CNS demyelination was observed in the placebo maintenance group in a patient who received SIMPONI 400/200 mg during induction. Liver Enzyme Elevations There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF blockers. In adult controlled Phase 3 trials of SIMPONI in patients with RA, PsA, and AS through Week 16, ALT elevations ≥ 5 × ULN occurred in 0.2% of control-treated patients and 0.7% of SIMPONI-treated patients and ALT elevations ≥ 3 × ULN occurred in 2% of control-treated patients and 2% of SIMPONI-treated patients. Since many of the patients in the Phase 3 trials for RA, PsA, and AS were also taking medications that cause liver enzyme elevations (e.g., NSAIDs, MTX), the relationship between SIMPONI and liver enzyme elevation is not clear. In Trials UC-1, UC-2, and UC-3, the incidence of ALT elevations ≥ 5 × ULN was similar in SIMPONI-treated patients and placebo-treated patients, or approximately 1%, with an average duration of follow-up of 46 weeks and 18 weeks, respectively. ALT elevations ≥ 3 × ULN occurred in 2.0% of SIMPONI-treated patients compared with 1.5% of placebo-treated patients with an average duration of follow-up of 46 weeks and 18 weeks, respectively. Autoimmune Disorders and Autoantibodies In the adult controlled Phase 3 trials in patients with RA, PsA, and AS through Week 14, there was no association of SIMPONI treatment and the development of newly positive anti-dsDNA antibodies. In Phase 3 trials in RA, PsA, and AS through 1 year of follow-up, 4.0% of SIMPONI-treated patients and 2.6% of control patients were newly antinuclear antibody (ANA)-positive (at titers of 1:160 or greater). The frequency of anti-dsDNA antibodies at 1 year of follow-up was uncommon in patients who were anti-dsDNA negative at baseline. Through Week 60 of the UC trials (Trials UC-1, UC-2, and UC-3), 3.5% of patients who received SIMPONI induction and 100 mg during maintenance were newly ANA-positive (at titers of 1:160 or greater) compared with 3.5% of patients who received SIMPONI induction and placebo during the maintenance period in Trial UC-2. The frequency of anti-dsDNA antibodies at 1 year of follow-up in patients who were anti-dsDNA negative at baseline was 0.5% in patients receiving SIMPONI induction and 100 mg during maintenance compared with 0% in patients who received SIMPONI induction and placebo during maintenance. Injection Site Reactions In adult controlled Phase 3 trials through Week 16 in RA, PsA and AS, 6% of SIMPONI-treated patients had injection site reactions compared with 2% of control-treated patients. The majority of the injection site reactions were mild and the most frequent manifestation was injection site erythema. In Trial UC-1, 3.4% of SIMPONI-treated patients had injection site reactions compared with 1.5% in control-treated patients. The majority of the injection site reactions were mild and moderate and the most frequent manifestation was injection site erythema. In adult controlled Phase 2 and 3 trials in RA, PsA, AS, no patients treated with SIMPONI developed anaphylactic reactions. Other Adverse Reactions Table 2 summarizes the adverse drug reactions that occurred at a rate of at least 1% in the SIMPONI ± DMARD group and with a higher incidence than in the placebo ± DMARD group during the controlled period of the 5 pooled Phase 3 trials through Week 16 in adult patients with RA, PsA, and AS.

Table 2: Adverse Drug Reactions Reported by ≥ 1% of SIMPONI-Treated Patients and with a Higher Incidence Than Placebo-Treated Patients in the Adult Phase 3 Trials of RA, PsA, and AS through Week 16 Patients may have taken concomitant MTX, sulfasalazine, hydroxychloroquine, low dose corticosteroids (≤ 10 mg of prednisone/day or equivalent), and/or NSAIDs during the trials). SIMPONI ± DMARDs Placebo ± DMARDs Patients treated 1659 639 Adverse Reaction Infections and infestations Upper respiratory tract infection (nasopharyngitis, pharyngitis, laryngitis, and rhinitis) 16% 13% Viral infections (such as influenza and herpes) 5% 3% Bronchitis 2% 1% Superficial fungal infections 2% 1% Sinusitis 2% 1% General disorders and administration site conditions Injection site reaction (injection site erythema, urticaria, induration, pain, bruising, pruritus, irritation, paresthesia) 6% 2% Investigations Alanine aminotransferase increased 4% 3% Aspartate aminotransferase increased 3% 2% Vascular disorders Hypertension 3% 2% Nervous system disorders Dizziness 2% 1% Paresthesia 2% 1% Gastrointestinal disorders Constipation 1% <1% Less Common Clinical Trial Adverse Drug Reactions Adverse drug reactions that occurred <1% in adult SIMPONI-treated patients in the RA, PsA and AS clinical trials that do not appear in the Warnings and Precautions section included the following events listed by system organ class: Infections and infestations: Septic shock, atypical mycobacterial infection, pyelonephritis, arthritis bacterial, bursitis infective Neoplasms benign, malignant and unspecified: Leukemia Skin and subcutaneous tissue disorders: Psoriasis (new onset or worsening, palmar/plantar and pustular), vasculitis (cutaneous) Vascular disorders: Vasculitis (systemic) Adults and Pediatric Patients Weighing at least 15 kg with Ulcerative Colitis In general, adverse reactions reported in adult patients with UC in Trials UC-1, UC-2, and UC-3 were similar to those reported in clinical trials of patients with RA, PsA, and AS. Adverse reactions reported in the clinical trial of pediatric patients weighing at least 15 kg with UC were also similar to those reported in clinical trials of adults with UC and the other indicated populations. Additional adverse reactions reported in at least 10% of pediatric patients in the trial were headache (17%) and pyrexia (10%).

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of golimumab. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to SIMPONI exposure.

Immune system disorders: Serious systemic hypersensitivity reactions (including anaphylactic reaction), sarcoidosis Neoplasms benign, malignant and unspecified: Melanoma, Merkel cell carcinoma Respiratory, thoracic and mediastinal disorders: Interstitial lung disease Skin and subcutaneous tissue disorders: Skin exfoliation, lichenoid reactions, rash, bullous skin reactions