EULAR News: Tremyfa Data Shows Sustained Improvements in PsA
Tremfya provides sustainable improvements in all minimal disease activity domains through week 48 in adults with active PsA who previously had an inadequate response to one to two TNF blockers.
Tremfya (guselkumab) provides sustainable improvements in all minimal disease activity (MDA) domains through week 48 in adults with active psoriatic arthritis (PsA) who previously had an inadequate response to one to two tumor necrosis factor inhibitors (TNFi-IR), according to new data from the Phase 3b COSMOS clinical trial.
In a separate post-hoc analysis of the Phase 3 DISCOVER-1 and DISCOVER-2b clinical trial findings, Tremfya was shown to be associated with prompt and sustained improvements in all identified determinants. This analysis also identified factors that influenced disagreement between patient and physician global assessments (GA), such as patient-reported pain, physical aspects of health-related quality of life and fatigue. Tremfya is the first and only fully human selective interleukin (IL)-23 inhibitor therapy approved for the treatment of adult patients living with active PsA.
These study results are being presented by Janssen at the 2023 Annual European Congress of Rheumatology (EULAR) meeting in Milan, Italy.
A previous study has shown that sustained MDA is typically only achieved by a minority of patients receiving biologic therapy for active PsA. However, in a post-hoc analysis of the Phase 3b COSMOS clinical trial, Tremfya provided sustained improvement in all MDA domains from baseline through week 48 in adult patients living with active PsA and who were inadequate responders to one to two TNFis (n=189).
Overall response rates at week 24 and week 48 were Psoriasis Area and Severity Index (PASI) (66.8/81.5%), Leeds Enthesitis Index (LEI) (74.5/79.8%), swollen joint count (SJC) (46.2/63.0%), patient GA (24.5/39.9%), Health Assessment Questionnaire – Disability Index (HAQ-DI)f (26.1/37.0%), patient pain (14.7/30.6%) and tender joint count (TJC) (14.7/28.3%), respectively.
Physician-reported domains (LEI, PASI and SJC) were achieved faster than patient-driven domains (patient GA, HAQ-DI, patient pain and TJC).
“Assessing patient-reported symptoms is a vital part of our research that helps us to address unmet needs and provide treatments that can improve outcomes,” says Laura Coates, M.D., Ph.D., Senior Clinical Research Fellow at the University of Oxford, in a news release. “These results advance our understanding of the psoriatic arthritis patient experience and will help healthcare professionals develop individualized treatment plans that can target debilitating symptoms and, ultimately, aim to improve quality of life for people living with psoriatic arthritis.”
The importance of a personalized approach to PsA treatment that prioritizes shared decision-making and open dialogue is reinforced in a separate post-hoc analysis of the Phase 3 DISCOVER-1 and DISCOVER-2 studies, which identified differences between patient GA and physician GA. The results showed that while scores were aligned across most factors, patients weighed pain, fatigue and physical health higher than physicians. Tremfya was associated with prompt and sustained improvements in all identified determinants, including those driving higher patient versus physician scores, such as patient-reported pain, physical aspects of health-related quality of life, and fatigue.
At baseline, patient GA and physician GA scores were similar in most instances (61.2%) with 23.2% of cases characterized by a patient GA score higher than a physician GA score. Higher patient scores meant the patient considered this aspect of their disease to be worse than the physician. Fully 15.7% of cases had a physician GA score higher than patient GA.
The proportion of patients with higher patient GA score than physician GA score increased to 39.1% at week 24, while the proportion with higher physician GA scores decreased to 11.2%. The main determinant of higher patient scores was patient pain, with additional factors including worse physical health-related quality of life at baseline and worse fatigue at week 24. Conversely, physicians emphasized objective disease measures, including SJCs, TJCs and elevated C-reactive protein when assessing patient disease status.
“Our continued research underscores Janssen’s commitment to not only provide therapeutic options for psoriatic disease, but also to better understand and support the pressing needs of the patients we serve,” says Terence Rooney, M.D., Ph.D., Vice President, Rheumatology and Maternal-Fetal Immunology Disease Area Leader, Janssen Research & Development, LLC. “Active psoriatic arthritis is a challenging, chronic disease, so these findings have important implications for patients and their providers as they work together to address the full spectrum of disease symptoms, including patient-five criteria: patient GA, physician GA, functional ability measure (HAQ-DI), patient-reported pain using a visual analog scale, and erythrocyte sedimentation reported outcomes, with the goal of achieving long-term relief.”
About COSMOS
COSMOS was a Phase 3b, multicenter, randomized, double-blind, placebo- controlled study to evaluate the efficacy and safety of Tremfya, administered by subcutaneous injection, in 285 adult patients with active PsA and inadequate response to TNFi therapy.The primary endpoint was ACR20 response at week 24.8 The primary endpoints results were announced in June 2021. Participants were randomized (2:1) to receive Tremfya 100 mg at weeks 0, 4 and every eight weeks thereafter, or placebo. The study included two periods: a 24-week double-blind, placebo-controlled period for the primary analysis of the efficacy and safety of Tremfya compared with placebo and a 32-week active-treatment and safety follow-up period for additional analysis of the efficacy and safety of Tremfya. Through week 48, non-responder imputation rules were used for missing data (after the application of treatment failure rules). Safety was monitored throughout the study to week 56.8 In patients with active PsA and prior inadequate response to ≤2 TNFi, Tremfya demonstrated an adverse event (AE) profile consistent with placebo through week 24, with no increase in AEs through one year of treatment. As such, the COSMOS safety results were consistent with the known safety profile of Tremfya in biologic-naïve patients with PsA.
About DISCOVER-1
DISCOVER-1 was a Phase 3, multicenter, randomized, double-blind study evaluating the efficacy and safety of TREMFYA administered by subcutaneous injection in participants with active PsA, including those previously treated with one to two TNFis. DISCOVER-1 evaluated 383 participants who were treated and followed through approximately one year. The study consisted of a screening phase of up to six weeks, a blinded treatment of 52 weeks that included a placebo-controlled period from week 0 to week 24, and a blinded active treatment period from week 24 to week 52. In a mixed population of patients with active PsA (69% bio-naïve; 31% TNFi-experienced), Tremfya demonstrated an AE profile consistent with placebo through week 24, with no increase in time-adjusted rates of AEs through one year of treatment, regardless of prior TNFi exposure. It also included a safety follow-up phase through week 60 (i.e., approximately 12 weeks from the last administration of study agent at week 48). Efficacy, safety, pharmacokinetic, immunogenicity and biomarker evaluations were performed in the study on a defined schedule. The primary endpoint was response of ACR20 at week 24.
About DISCOVER-2
DISCOVER-2 was a Phase 3, multicenter, randomized, double-blind study evaluating the efficacy and safety of Tremfya administered by subcutaneous injection in biologic-naïve patients with active PsA. DISCOVER-2 evaluated 741 participants who were treated and followed through approximately two years. The study consisted of a screening phase of up to six weeks, a blinded treatment phase of approximately 100 weeks that included a placebo-controlled period from week 0 to week 24 and a blinded active treatment period from week 24 to week 100. It also included a safety follow-up phase through week 112 (i.e., approximately 12 weeks after the last administration of study agent at week 100). In a large cohort of biologic-naïve patients with active PsA, Tremfya demonstrated an AE profile consistent with placebo through week 24, with no increase in time-adjusted AE rates through two years of Tremfya treatment. Clinical efficacy, radiographic efficacy, health economics, safety, pharmacokinetics, immunogenicity, biomarker, and pharmacogenomics evaluations were performed in the study on a defined schedule.17 The primary endpoint was response of ACR20 at week 24.