Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

Jonathan Kay; Roy Fleischmann; Edward Keystone; Elizabeth C Hsia; Benjamin Hsu; Yiying Zhou; Neil Goldstein; Jürgen Braun

doi:10.3899/jrheum.160420

Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

J Rheumatol. 2016 Dec;43(12):2120-2130. doi: 10.3899/jrheum.160420. Epub 2016 Nov 1.

Authors

Jonathan Kay^{1

2}, Roy Fleischmann^{3

4}, Edward Keystone^{3

4}, Elizabeth C Hsia^{3

4}, Benjamin Hsu^{3

4}, Yiying Zhou^{3

4}, Neil Goldstein^{3

4}, Jürgen Braun^{3

4}

Affiliations

¹ From the Division of Rheumatology, Department of Medicine, UMass Memorial Medical Center, and University of Massachusetts Medical School, Worcester, Massachusetts; Rheumatology, University of Texas Southwestern Medical Center and Metroplex Clinical Research Center, Dallas, Texas; Janssen Research and Development LLC, Spring House; University of Pennsylvania, Philadelphia, Pennsylvania, USA; Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada; Rheumatology, Rheumazentrum Ruhrgebeit, Herne, Germany. jonathan.kay@umassmemorial.org.
² J. Kay, MD, Division of Rheumatology, and Department of Medicine, UMass Memorial Medical Center, University of Massachusetts Medical School; R. Fleischmann, MD, Rheumatology, University of Texas Southwestern Medical Center, and Metroplex Clinical Research Center; E. Keystone, MD, FRCP(C), Division of Rheumatology, University of Toronto; E.C. Hsia, MD, Janssen Research and Development LLC, and University of Pennsylvania; B. Hsu, MD, PhD, Janssen Research and Development LLC, and University of Pennsylvania; Y. Zhou, PhD, Janssen Research and Development LLC; N. Goldstein, MD, Janssen Research and Development LLC; J. Braun, MD, Rheumatology, Rheumazentrum Ruhrgebeit. jonathan.kay@umassmemorial.org.
³ From the Division of Rheumatology, Department of Medicine, UMass Memorial Medical Center, and University of Massachusetts Medical School, Worcester, Massachusetts; Rheumatology, University of Texas Southwestern Medical Center and Metroplex Clinical Research Center, Dallas, Texas; Janssen Research and Development LLC, Spring House; University of Pennsylvania, Philadelphia, Pennsylvania, USA; Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada; Rheumatology, Rheumazentrum Ruhrgebeit, Herne, Germany.
⁴ J. Kay, MD, Division of Rheumatology, and Department of Medicine, UMass Memorial Medical Center, University of Massachusetts Medical School; R. Fleischmann, MD, Rheumatology, University of Texas Southwestern Medical Center, and Metroplex Clinical Research Center; E. Keystone, MD, FRCP(C), Division of Rheumatology, University of Toronto; E.C. Hsia, MD, Janssen Research and Development LLC, and University of Pennsylvania; B. Hsu, MD, PhD, Janssen Research and Development LLC, and University of Pennsylvania; Y. Zhou, PhD, Janssen Research and Development LLC; N. Goldstein, MD, Janssen Research and Development LLC; J. Braun, MD, Rheumatology, Rheumazentrum Ruhrgebeit.

PMID: 27803138
DOI: 10.3899/jrheum.160420

Abstract

Objective: Assess 5-year golimumab (GOL) safety in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).

Methods: Subcutaneous (SC) GOL (50 mg or 100 mg every 4 weeks) was evaluated in phase 3 trials of patients with active RA, PsA, and AS. Safety data through Year 5 were pooled across 3 RA trials [1 each evaluating methotrexate (MTX)-naive, MTX-experienced, and antitumor necrosis factor (TNF)-experienced patients], 1 PsA trial, and 1 AS trial. Data summarized was derived from both placebo-controlled (through weeks 24-52) and uncontrolled study periods. For adverse events (AE) of special interest [serious infections (SI), opportunistic infections (OI), deaths, malignancies, demyelination, tuberculosis (TB)], incidence per 100 patient-years (pt-yrs) was determined.

Results: Across all trials, 639 patients received placebo and 2228 received SC GOL 50 mg only (n = 671), 50 mg and 100 mg (n = 765), or 100 mg only (n = 792). Safety followup extended for averages of 28.5 and 203.2 weeks for placebo and GOL, respectively. Respective placebo and GOL AE incidence/100 pt-yrs (95% CI) through Year 5 were 4.86 (2.83-7.78) and 3.29 (2.92-3.69) for SI, 0.00 (0.00-0.86) and 0.23 (0.14-0.35) for TB, 0.00 (0.00-0.86) and 0.22 (0.13-0.34) for OI, 0.00 (0.00-0.86) and 0.10 (0.05-0.20) for lymphoma, 0.00 (0.00-0.86) and 0.08 (0.03-0.17) for demyelination, and 0.29 (0.01-1.59) and 0.41 (0.29-0.57) for death. TB, OI, lymphoma, and demyelination incidence appeared to be higher among patients receiving GOL 100 mg only.

Conclusion: SC GOL safety through Year 5 remained consistent with previously reported Year 3 findings and with other TNF antagonists. Numerically higher incidences of TB, OI, lymphoma, and demyelination were observed with 100 mg versus 50 mg. Clinicaltrials.gov identifiers: NCT00264537 (GO-BEFORE), NCT00264550 (GO-FORWARD), NCT00299546 (GO-AFTER), NCT00265096 (GO-REVEAL), and NCT00265083 (GO-RAISE).

Keywords: ADVERSE EVENTS; ANTITUMOR NECROSIS FACTOR; CLINICAL TRIAL; LYMPHOMA; MALIGNANCY; TUBERCULOSIS.

MeSH terms

Antibodies, Monoclonal / administration & dosage
Antibodies, Monoclonal / adverse effects*
Antibodies, Monoclonal / therapeutic use
Antirheumatic Agents / administration & dosage
Antirheumatic Agents / adverse effects*
Antirheumatic Agents / therapeutic use
Arthritis, Psoriatic / drug therapy*
Arthritis, Rheumatoid / drug therapy*
Drug Therapy, Combination
Humans
Injections, Subcutaneous
Methotrexate / therapeutic use
Spondylitis, Ankylosing / drug therapy*
Treatment Outcome

Substances

Antibodies, Monoclonal
Antirheumatic Agents
golimumab
Methotrexate

Associated data

ClinicalTrials.gov/NCT00265083
ClinicalTrials.gov/NCT00265096
ClinicalTrials.gov/NCT00264537
ClinicalTrials.gov/NCT00299546
ClinicalTrials.gov/NCT00264550