PharmaShots Interview: Janssen’s Soumya D. Chakravarty Shares Insights on Tremfya (guselkumab) for the Treatment of Active Psoriatic Arthritis

In an interview with PharmaShots, Soumya D. Chakravarty, Senior Director, Strategic Lead, Rheumatology Therapeutic Area at Janssen shared his views on the data of Tremfya in the P-IIIb (COSMOS) trial for the treatment of active psoriatic arthritis, published in the Annals of the Rheumatic Diseases

The P-IIIb (COSMOS) trial evaluates Tremfya (100mg) vs PBO in a ratio (2:1) in 285 patients with active PsA and IR to TNFi therapy
The study met its 1EPs i.e., patients achieved 20% improvement in ACR20 response @24wk. (44.4% vs 19.8%), patients had higher ACR20 & ACR50 response rates @4 & 8wk., improvement in joint signs & symptoms, was maintained & increased over time, complete skin clearance (30.8% vs 3.8%), DAPSA remission (5.3% vs 2.1%), improvements in physical function (37.5% vs 16.1%)
Additionally, response rates continued to improve @1yr. with 57.7% of patients achieving ACR20 with a similar safety profile, low rates of AEs leading to discontinuation response

Tuba: Enlist the key points of P-III Tremfya data published in the Annals of the Rheumatic Diseases.

Soumya Chakravarty: The Phase 3b COSMOS study evaluated the selective interleukin(IL)-23 inhibitor TREMFYA® (guselkumab) in adults with active psoriatic arthritis (PsA) who had demonstrated inadequate response or intolerance (IR) to tumor necrosis factor inhibition (TNFi), an often more difficult to treat population. The results showed that significantly higher proportions of TNFi-IR patients treated with TREMFYA had improvement in joint signs and symptoms and complete skin clearance versus placebo at week 24. Additionally, TREMFYA-treated patients sustained or numerically increased these improvements in the signs and symptoms of active PsA through one year (week 48).

Tuba: Discuss the study design and clinical outcomes of the COSMOS study?

Soumya Chakravarty: COSMOS was a Phase 3b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of TREMFYA in 285 patients with active PsA and IR to TNFi therapy. The primary endpoint was an American College of Rheumatology (ACR)20 response at week 24. Participants were randomized (2:1) to receive TREMFYA 100 mg subcutaneously at weeks 0, 4, and every 8 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 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 (NRI) rules were used for missing data (after the application of treatment failure rules [TFR]). Safety was monitored throughout the study to week 56.

Tuba: Give a few pieces of evidence that showed Tremfya is effective in treating patients with various manifestations of active psoriatic arthritis even when TNF inhibitor treatment has failed.

Soumya Chakravarty: In the COSMOS results, which evaluated TNFi-IR patients, TREMFYA showed sustained efficacy across the varied symptoms of active PsA, including joint, skin, and axial symptoms, fatigue, and health-related quality of life (HRQoL).

The study achieved its primary endpoint at week 24, with 44.4 percent of patients who received TREMFYA versus 19.8 percent of patients who received placebo achieving at least 20 percent improvement in the ACR20 criteria. ACR20 response rates continued to improve during the first year across different analysis sets: 57.7 percent of TREMFYA patients at week 48 utilizing stringent NRI criteria, and >80 percent of week 24 responders maintained response at week 48. At week 48, more than half of patients (53.4 percent) receiving TREMFYA achieved complete skin clearance, as measured by the Psoriasis Area Severity Index (PASI) 100.

At week 24, higher proportions of TREMFYA-treated patients versus placebo (37.5 percent vs 16.1 percent) achieved clinically meaningful improvements in physical function (Health Assessment Questionnaire Disability Index [HAQ-DI]), which increased to 53.4 percent at week 48. TREMFYA-treated patients also reported better physical aspects of HRQoL (Short Form [SF]-36 Physical Component Summary [PCS] scores) versus placebo. At week 24, higher proportions of TREMFYA-treated patients achieved a ≥4-point increase in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) versus placebo (42.9 percent vs 20.8 percent), reflecting a clinically meaningful improvement in fatigue. This response also increased over time to 55.6 percent of TREMFYA patients at week 48.

Tuba: Provide the clinical explanation to the statement: “Tremfya showed Joint Symptom Improvement in Active Psoriatic Arthritis patients’’

Soumya Chakravarty: In clinical terms, improvement in joint signs and symptoms of active PsA is demonstrated through evaluation using the ACR20/50/70 response criteria. When we say that TREMFYA-treated patients showed joint symptom improvement, we’re saying that they showed at least a 20%, 50%, or 70% improvement in ACR response criteria. An ACR20 response is defined as both improvement of 20% in the number of tender and swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

44.4 percent of patients who received TREMFYA achieved an ACR20 response at week 24, rising to 57.7 percent at week 48 when using a conservative form of statistical analysis (NRI). TREMFYA-treated patients also showed higher ACR20 and ACR50 response rates compared to placebo as early as weeks four and eight, respectively – meaning they’re showing improvements in the joint signs and symptoms of PsA earlier as well as more often.

Tuba: What are the key features of Tremfya? Why is it considered to be the effective treatment of difficult to treat PsA?

Soumya Chakravarty: TREMFYA is the first and only approved fully human monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. Because IL-23 is an important driver of the pathogenesis of inflammatory diseases like active PsA and moderate to severe plaque PsO, TREMFYA has shown strong efficacy in providing these patients with complete skin clearance, joint and axial symptom improvements, and a consistent, established safety profile across both disease areas.

Tuba: What are the other comorbidities related to PsA? How Tremfya help in reducing those?

Soumya Chakravarty: In patients with active PsA, comorbidities such as obesity, cardiovascular diseases, anxiety, and depression are often present. There is also a relationship to PsO – studies show up to 30 percent of people with plaque PsO also develop active PsA. TREMFYA is approved in the U.S., Canada, Japan, and a number of other countries worldwide for the treatment of adults with moderate to severe plaque PsO who are candidates for systemic therapy or phototherapy, as well as for the treatment of adult patients with active PsA. Janssen continues to investigate the effect TREMFYA can have on inhibiting radiographic progression in peripheral joints in PsA, ameliorating both axial symptoms and inflammation of PsA, as well as related conditions like inflammatory bowel disease that act along the same immune pathway.

Tuba: Discuss the journey of Janssen in terms of its efforts in curbing difficult to treat Psoriatic Arthritis.

Soumya Chakravarty: Since the recent discovery of the importance of the IL-23 pathway in immune-mediated diseases, Janssen has worked to investigate the ways this and other pathways are involved in inflammatory responses across multiple disease areas. By applying our insights in PsA and PsO, we are learning about how patients respond to treatment and working to develop more safe, effective options to bring the goal of full remission into view.

Tuba: Highlight the digital initiatives of Janssen for the PsA population.

Soumya Chakravarty: In all our work and research, Janssen is focused on developing digital tools that can improve assessments for patients and physicians, including investing in remote technologies that facilitate easier data capture for clinical trials and support patient-reported outcomes.

Source: Pexels

About Author:

Soumya D. Chakravarty is the Senior Director, Strategic Lead, Rheumatology Therapeutic Area at Janssen. Soumya was an active clinician and clinical investigator with a focus on inflammatory arthritis disease pathogenesis. He received his B.S. in Biochemistry from the University of Michigan, MD, and his Ph.D. from the Albert Einstein College of Medicine of Yeshiva University in NY. He completed his internal medicine residency at New York-Presbyterian Hospital—Weill Cornell Medical College and fellowship/instructorship in rheumatology at Hospital for Special Surgery, both in NY