Tremfya (guselkumab) demonstrated improvements in multiple clinical outcomes including joint symptoms, skin symptoms, soft tissue inflammation, physical function and reduction in radiographic progression at week 52 in adult patients with active psoriatic arthritis (PsA), according to data from two Phase 3 clinical trials, DISCOVER-1 and DISCOVER-2.
These findings are being presented at the 2020 European League Against Rheumatism (EULAR) E-Congress.
The Janssen Pharmaceutical Companies of Johnson & Johnson’s Tremfya is currently not approved for the treatment of PsA in the U.S. Data from the two studies in the DISCOVER program formed the basis of the September 13, 2019 supplemental Biologics License Application submission to the U.S. Food and Drug Administration (FDA) for approval of Tremfya and primary endpoint results were recently published in The Lancet.
"Those who are living with active psoriatic arthritis are faced with debilitating symptoms and inflammation which may ultimately lead to irreversible damage to the joints," says Christopher Ritchlini, M.D., M.P.H., Chief of the Division of Allergy, Immunology and Rheumatology and Director of the Clinical Immunology Research Center at the University of Rochester Medical Center in Rochester, New York and lead investigator of the DISCOVER-1 study, in a news release. "Findings from the DISCOVER-1 and DISCOVER-2 studies are encouraging for patients and physicians alike who may be seeking new treatment options that utilize mechanisms of action different to anti-tumor necrosis factor (TNF) alpha biologics to combat the multi-faceted combination of symptoms presented by psoriatic arthritis."
DISCOVER-1 and DISCOVER-2 evaluated the efficacy and safety of Tremfya compared to placebo. DISCOVER-1 included patients who were biologic-naïve or had previously been exposed to anti-TNF alpha biologics. DISCOVER-2 included patients who were biologic-naïve only; it also assessed radiographic progression of joint damage. In both studies, patients were randomized to Tremfya 100 mg every 4 weeks (q4w) or every 8 weeks (q8w) for one year, or to placebo with crossover to Tremfya q4w at week 24 through one year.
In both studies, American College of Rheumatology (ACR) response rates at week 52 included non-responder imputation (NRI) data, which categorized patients who discontinued the study as non-responders from week 24 to 52.
In DISCOVER-1, data demonstrated that at week 52:1
- 73 percent of Tremfya q4w patients and 60 percent of Tremfya q8w patients achieved ACR20; 54 percent of Tremfya q4w patients and 39 percent of Tremfya q8w patients achieved ACR50 (NRI).
- Among patients who had clinically relevant psoriasis at baseline, 83 percent of Tremfya q4w patients, 69 percent of Tremfya q8w patients and 82 percent of patients who crossed over from placebo to Tremfya q4w achieved clear or almost clear skin with at least a 2-grade improvement from baseline as measured by the Investigator Global Assessment (IGA) score (observed data).6
In DISCOVER-2, data demonstrated that at week 52:2
- 71 percent of Tremfya q4w patients and 75 percent of Tremfya q8w patients achieved ACR20; 46 percent of Tremfya q4w patients and 48 percent of Tremfya q8w patients achieved ACR50 (NRI).
- Among patients who had clinically relevant psoriasis at baseline, 84 percent of Tremfya q4w patients, 77 percent of Tremfya q8w patients and 84 percent of patients who crossed over from placebo to Tremfya q4w achieved clear or almost clear skin with at least a 2-grade improvement from baseline as measured by the IGA score (observed data).6
- Tremfya q4w and q8w demonstrated sustained improvements in inhibition of radiographic progression of joint structural damage through week 52 (observed data).
The DISCOVER studies also showed improvements in multiple secondary endpoints at week 52 compared with week 24, including ACR70 response, resolution of soft tissue inflammation (enthesitis and dactylitis), disease activity score (DAS-28) (C-Reactive Protein [CRP])10, (minimal disease activity [MDA]), (very low disease activity [VLDA]), improvement in physical function (Health Assessment Questionnaire Disability Index [HAQ-DI])13, general health outcomes (SF-36 Physical Component Summary [PCS] and Mental Component Summary [MCS]).
In both studies, Tremfya was well-tolerated through study completion, and observed 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. There were no reported deaths in Tremfya-treated patients and no Tremfya-treated patient had inflammatory bowel disease, opportunistic infections, active tuberculosis or anaphylactic or serum sickness-like reactions.
"Efficacy of Tremfya in psoriatic arthritis was previously demonstrated to be superior to placebo at week 24. These new data show that efficacy is maintained to week 52 with safety data that are consistent with the well-established profile of Tremfya in psoriasis," says Alyssa Johnsen, M.D., Ph.D., Vice President, Rheumatology Disease Area Leader, Janssen Research & Development, LLC. "We are excited to share the data on Tremfya in psoriatic arthritis as we continue to advance our research in this disease and bring more treatment options to psoriatic arthritis patients in need."
In a separate study, data from DISCOVER-1 and DISCOVER-2 were analyzed as part of a network meta-analysis that compared the efficacy and safety of Tremfya to other targeted biologic therapies for PsA. Twenty-six Phase 3 studies were included comparing the impact of 13 targeted therapies for PsA on ACR 20/50/70 response, Psoriasis Area Severity Index (PASI) 75/90/100 response, HAQ-DI score, resolution of enthesitis, resolution of dactylitis, AEs and serious AEs.
DISCOVER-1 is a randomized, double-blind, multicenter Phase 3 study evaluating the efficacy and safety of TREMFYA administered by subcutaneous (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.