The IL-23 blocker Tremfya (guselkumab) improves fatigue in adult patients with active psoriatic arthritis (PsA) and this response is maintained through 52 weeks of active treatment, according to data from two Phase 3 clinical trials, DISCOVER-1 and DISCOVER-2.
Tremfya improved fatigue during the placebo-controlled periods of both studies at week 24, and through one year of active treatment as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale. In both studies, Tremfya had positive effect on fatigue, in addition to other clinical outcomes, including ACR20 response.
The findings are slated to be presented during ACR Convergence 2020, the American College of Rheumatology (ACR) virtual annual meeting.
"Fatigue associated with psoriatic arthritis can have a serious impact on patients' health-related quality of life and can lead to social isolation and loss of employment," says Proton Rahman, M.D., Professor of Medicine, Rheumatology, Memorial University in Newfoundland, Canada and presenting author of the study, in a news release. "These findings from the DISCOVER-1 and DISCOVER-2 studies showing an improvement in fatigue a full year into treatment with Tremfya add to the previously presented 52-week data demonstrating an improvement in joint and skin symptoms. Considered together, the data are encouraging for active psoriatic arthritis patients who struggle with multiple symptoms."
In both DISCOVER-1 and DISCOVER-2 clinical trials:
- The FACIT-Fatigue Scale, a validated patient-reported outcomes instrument, was used to assess fatigue and its impact on daily activities and function over the prior 7 days. Scale scores range from 0 to 52, with the higher score denoting less fatigue. A change of ≥4 points is considered clinically meaningful.
- At baseline in both studies, the mean FACIT-Fatigue scores were 30.4 (10.4) and 29.7 (9.7), respectively, indicating that patients with active PsA experienced fatigue worse than the general population [43.6 (9.4)].
- At week 24 in both studies, treatment with Tremfya led to greater improvements in FACIT-Fatigue scores compared with placebo, as early as week 16 in DISCOVER-1 and week 8 in DISCOVER-2, with 54%-63% of Tremfya patients achieving clinically meaningful improvement (≥4 points) in FACIT-Fatigue compared with 35%-46% of placebo patients (unadjusted p≤0.003).
- FACIT-Fatigue least squares (LS) mean changes from baseline were 5.6 and 5.8 for q8w and every four weeks (q4w), respectively, compared with 2.2 for placebo in DISCOVER-1, and 7.6 and 7.1 for q8w and q4w, respectively, compared with 3.6 for placebo in DISCOVER-2.
- After crossing over to Tremfya q4w at week 24, patients who had previously been on placebo achieved FACIT-Fatigue scores comparable to those of Tremfya patients through week 52 (mean change from baseline of 6.6 vs. 6.9, respectively, in DISCOVER-1, and 7.5 vs. 7.7, respectively, in DISCOVER-2).
- At 52 weeks, 61%-70% of both Tremfya patients and those who crossed over from placebo to Tremfya after 24 weeks achieved a clinically meaningful improvement in FACIT-Fatigue score.
In both studies, Tremfya was well-tolerated through study completion, and adverse events (AEs) were generally consistent with previous studies of Tremfya and current prescribing information. Serious AEs and serious infections occurred in 4 percent and 1 percent of Tremfya -treated patients, respectively, in both DISCOVER-1 and DISCOVER-2.
"Data from the DISCOVER-1 and DISCOVER-2 studies demonstrating TREMFYA reduced fatigue through 52 weeks provide evidence of an additional treatment benefit for patients with active PsA," says Alyssa Johnsen, M.D., Ph.D., Vice President, Rheumatology Disease Area Leader, Janssen Research & Development, LLC. "The positive outcomes in fatigue assessment add to the body of data for Tremfya, which has shown improvements in multiple clinical outcomes including joint symptoms, skin symptoms, soft tissue inflammation, and physical function."
Tremfya was approved in July 2020 by the U.S. FDA for adult patients with active PsA, a chronic progressive disease characterized by painful joints and skin inflammation,and is the first and only therapy approved for active PsA to have improvement in fatigue as measured by FACIT-F in the product label. The approval was based on results from two pivotal Phase 3 clinical trials, DISCOVER-1 and DISCOVER-2, which evaluated the efficacy and safety of Tremfya administered by SC injection in adults with active PsA compared to placebo, and showed that a significant percentage of patients treated with Tremfya reached the studies' primary endpoint of ACR20 at 24 weeks. Recently announced data showed that Tremfya demonstrated improvements in multiple clinical outcomes including joint symptoms, skin symptoms, soft tissue inflammation, physical function, axial-related disease, and reduction in radiographic progression at week 52.
DISCOVER-1 is a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of Tremfya administered by SC injection in participants with active psoriatic arthritis including those previously treated with biologic anti-TNF alpha agent(s). DISCOVER-1 evaluated 381 participants and continued through approximately one year.
The study consisted of a screening phase of up to six weeks, a blinded treatment phase of 52 weeks that includes a placebo-controlled period from week 0 to week 24 and an active treatment period from week 24 to week 52. It also includes a safety follow-up phase of eight weeks after week 52 (week 52 to 60; 12 weeks from the last administration of study agent [at week 48] through to the final visit in the safety follow-up phase). Efficacy, safety, pharmacokinetic, immunogenicity and biomarker evaluations were performed in the study on a defined schedule.
DISCOVER-2 is a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of Tremfya administered by SC injection in subjects with active psoriatic arthritis. DISCOVER-2 is evaluating 739 participants and continuing through approximately two years.
The study consists of a screening phase of up to six weeks, a blinded treatment phase (approximately 100 weeks) that includes a placebo-controlled period from week 0 to week 24, and an active treatment period from week 24 to week 100. It also includes a safety follow-up phase of 12 weeks after the last administration of study agent. Efficacy, health economics, safety, pharmacokinetics, immunogenicity, biomarker, and pharmacogenomics evaluations are being performed in the study on a defined schedule.