Newly Published Network Meta-Analysis Found TREMFYA Ranked Highest for Overall Level of Skin Clearance, Provided Positive Joint Efficacy Among Active Psoriatic Arthritis Therapies

Janssen Pharmaceutical

SPRING HOUSE, PA The Janssen Pharmaceutical Companies of Johnson & Johnson recently announced a Network Meta-Analysis (NMA) comparing first-in-class interleukin (IL)-23 inhibitor TREMFYA® (guselkumab) to all advanced therapiesa approved for active psoriatic arthritis (PsA) using data from 33 Phase 3 randomized clinical trials (RCTs).1

The NMA concluded TREMFYA ranked highestb for skin clearance based on Psoriasis (PsO) Area Severity Index (PASI)c 90 response among 23 treatment regimens (15 unique treatments including IL-23 inhibitors like TREMFYA and risankizumab, subcutaneous [SC] tumor necrosis factor inhibitors [TNFi], and Janus kinase inhibitors [JAKi]).1 In terms of joint inflammation improvement, both TREMFYA dosing regimens (100 mg every four weeks [q4w] and every eight weeks [q8w])d were comparableb to most other treatments for the modified van der Heijde-Sharp (vdH-S)e score, and TREMFYA was generally comparableb to TNFi and most IL-17Ai for American College of Rheumatology (ACR) 20 response.1,f The analysis also confirmed the established safety profile of TREMFYA in active PsA.1 The NMA is being presented at the Maui Dermatology 2022 Meeting taking place January 24-28, 2022. TREMFYA is U.S. Food and Drug Administration (FDA) approved for administration as a 100 mg SC injection q8w, following two initial doses at weeks 0 and 4.2,d

“This comprehensive analytical approach helps to provide a useful comparative picture of available psoriatic arthritis medicines,” said Philip J. Mease,g M.D., Swedish Medical Center/Providence St. Joseph Health and University of Washington in SeattleWashington. “In my experience, thorough NMAs such as this one can help equip physicians to discuss treatment choices and therapeutic outcomes with their patients in daily practice.”

NMA is a structured, protocol-driven analytical process widely accepted and utilized by regulatory agencies, health technology assessment agencies and medical guideline committees to comparatively evaluate treatment options where head-to-head data are limited or unavailable.3-5 NMA is the most cited and the most comprehensive method available to compare studies indirectly; however, NMAs cannot replace and should not be considered the same as head-to-head clinical trials. In this NMA, the timing of primary endpoint assessment varied across RCTs, and placebo was used as the reference treatment throughout with the exception of two head-to-head studies.Baseline risk adjustment was used to account for heterogeneity across study populations. The NMA builds on previous analyses, including a 2021 publication in Rheumatology, and now incorporates all recent clinical data updates, including the COSMOS study of TREMFYA in PsA patients who had an inadequate response to TNFi, as well as data for two new comparators, the IL-23i risankizumab and the JAKi upadacitinib.1,6,7

NMA results showed:1

  • Skin Clearance: TREMFYA ranked first and secondb in PASI 90 response for q4wd and q8w dosing, respectively.
  • Joint Inflammation Improvement: TREMFYA was comparable to SC TNFi and most IL-17Ai, as measured by ACR20 response. While dosing frequency impacted modified vdH-S score,e both TREMFYA dosing regimens achieved improvements that were comparable to most treatments and both doses of TREMFYA ranked more highly on vdH-S score than risankizumab and upadacitinib.b
  • Low Numbers of Serious Adverse Events (SAEs): TREMFYA showed low rates of SAEs, with both dosing regimens ranking favorably among the 23 treatments for low rates of events. The number of SAEs for TREMFYA were consistent with the established TREMFYA safety profile.1
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“Psoriatic arthritis is a complex disease, and physicians must consider many factors when making treatment decisions, including the relative efficacy of therapies in treating both skin and joints, as well as established safety,” said Terence Rooney, M.D., Vice President, Rheumatology and Maternal-Fetal Immunology Disease Area Leader, Janssen Research & Development, LLC. “NMAs are a comprehensive, well-established approach, and can provide physicians with useful information on available therapies.”

TREMFYA was approved in the U.S. for the treatment of adult patients with moderate to severe plaque PsO in July 2017 and in July 2020 for adults with active PsA.2 The PsA approval was based on results from DISCOVER-1 and DISCOVER-2, which showed TREMFYA achieved the studies’ primary endpoint of ACR20 response at 24 weeks.8,9 A comprehensive analysis of DISCOVER-2 data was recently published in Arthritis & Rheumatology, representing the final results of the first-ever two-year clinical trial with an open-label extension investigating a selective IL-23 inhibitor therapy in active PsA.10

Janssen will present five additional posters at the Maui Dermatology Meeting, including the study design of APEX (NCT04882098),11 investigating the effect of TREMFYA on radiographic progression;h the design of the SOLSTICE trial (NCT04936308),12 which further evaluates TREMFYA efficacy for PsA patients with intolerance or inadequate response to TNF therapy; evidence of molecular and genetic distinctions between patients with axial PsA (axPsA) and ankylosing spondylitis and the significant pharmacodynamic effects of TREMFYA in axPsA patients; and real-world evidence for PsA patients initiating TREMFYA treatment in the CorEvitas Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry.

Notes:

a. Advanced therapies were defined as any targeted or biologic therapies for the treatment of PsA including: TNFi, JAKi, IL-17Ai, IL-12/23i, IL-23i, PDE4i, CTLA-4i, biologic biosimilar agents, and placebo/no treatment.1

b. Results are summarized by ranking treatments according to findings derived from NMAs. Conclusions (i.e., comparable) are based on an overlap of pairwise 95 percent credible intervals.1

c. PASI 90 is defined as at least 90 percent improvement from baseline in the PASI score. The PASI score grades the amount of surface area on each body region that is covered by PsO plaques and the severity of plaques for their redness, thickness, and scaliness.13 PASI 90 was not a controlled endpoint in DISCOVER-1 or -2.8,9

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d. TREMFYA q4w dosing is not currently FDA-approved.2

e. The PsA-modified vdH-S score combines erosion and joint space narrowing scores derived from radiographs of joints in body regions impacted by PsA.14 TREMFYA is not approved in the U.S. for inhibition of structural damage.2

f. ACR20 response is defined as both at least 20 percent improvement from baseline in the number of tender and number of swollen joints, and a 20 percent improvement from baseline in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure, visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.15

g. Dr. Mease is a paid consultant for Janssen. He has not been compensated for any media work.

h. Radiographic progression is a key indicator of structural damage, which includes erosion and joint space narrowing. Radiographic progression is not in the FDA label for TREMFYA.2

References

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  2. Food and Drug Administration. TREMFYA® Prescribing Information. Horsham, PA. 2017. Available at: https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TREMFYA-pi.pdf. Accessed January 2022.
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