ATLANTA – Guselkumab improved outcomes in psoriatic arthritis patients regardless of past treatment with tumor necrosis factor inhibitors in the phase 3 DISCOVER-1 trial.
The anti-interleukin-23p19 monoclonal antibody is approved in the United States for the treatment of moderate to severe plaque psoriasis (PsO).
Dr. Atul Deodhar
Benefits in psoriatic arthritis (PsA) were seen in both biologic-naive and tumor necrosis factor inhibitor (TNFi)–treated patients and occurred with both 4- and 8-week dosing regimens, Atul Deodhar, MD, reported during a plenary session at the annual meeting of the American College of Rheumatology.
For example, the primary endpoint of ACR 20 response at 24 weeks was achieved in 58.6% and 52.8% of patients randomized to receive 100 mg of guselkumab delivered subcutaneously either at baseline and every 4 weeks or at baseline, week 4, and then every 8 weeks, respectively, compared with 22.2% of those randomized to receive placebo, said Dr. Deodhar, professor of medicine at Oregon Health & Science University, Portland.
Greater proportions of patients in the guselkumab groups achieved ACR 20 response at week 16; ACR 50 response at weeks 16 and 24; ACR 70 response at week 24; Psoriasis Area and Severity Index 75, 90, and 100 responses at week 24; and minimal disease activity response at week 24, he said, adding that improvements were also seen with guselkumab versus placebo for the controlled major secondary endpoints of change from baseline in Health Assessment Questionnaire–Disability Index score, Short Form 36 Health Survey score, and investigator global assessment (IGA) of PsO response.
The response rates with guselkumab versus placebo were seen regardless of prior TNFi use, he said.
The study included 381 patients with active PsA, defined as three or more swollen joints, three or more tender joints, and C-reactive protein of 0.3 mg/dL or greater despite standard therapies. About 30% were exposed to up to two TNFi therapies and 10% were nonresponders or inadequate responders to those therapies.
Concomitant use of select nonbiologic disease-modifying antirheumatic drugs, oral corticosteroids, and NSAIDs was allowed, and patients with less than 5% improvement in tender plus swollen joints at week 16 could initiate or increase the dose of the permitted medications while continuing study treatment, Dr. Deodhar said.
The mean body surface area with PsO involvement was 13.4%; 42.5% of patients had an IGA of 3-4 for skin involvement. Mean swollen and tender joint counts were 9.8 and 19.3, respectively, indicating a population with moderate to severe disease, he added.
Serious adverse events, serious infections, and death occurred in 2.4%, 0.5%, and 0.3% of patients, respectively.
“Both guselkumab regimens were safe and well tolerated through week 24,” Dr. Deodhar said, noting that the safety profile was consistent with that established in the treatment of PsO and described in the label.
DISCOVER-1 was funded by Janssen Research & Development. Dr. Deodhar reported relationships (advisory board activity, consulting, and/or research grant funding) with several pharmaceutical companies including Janssen. Several coauthors are employees of Janssen.
SOURCE: Deodhar A et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 807.