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 Seattle, Washington. “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.1 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
“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.
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
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
- Mease, P., et al. Comparative Effectiveness of Guselkumab in Psoriatic Arthritis: Updates to a Systematic Literature Review and Network Meta-Analysis. Presented at Maui Derm, January 24-26, 2022.
- 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.
- Dias, S., et al. Evidence Synthesis for Decision Making 2. Medical Decision Making, 2012:33(5), 607–617. https://doi.org/10.1177/0272989×12458724
- Dias, S., et al. Evidence Synthesis for Decision Making 3. Medical Decision Making, 2013:33(5), 618–640. https://doi.org/10.1177/0272989×13485157
- Dias, S., et al. Evidence Synthesis for Decision Making 4. Medical Decision Making, 2013:33(5), 641–656. https://doi.org/10.1177/0272989×12455847
- Mease, P., et al. Comparative effectiveness of guselkumab in psoriatic arthritis: results from systematic literature review and network meta-analysis. Rheumatology (Oxford). 2021 May 14;60(5):2109-2121.
- Coates L, et al. Efficacy and Safety of Guselkumab in Patients With Active Psoriatic Arthritis who are Inadequate Responders to Tumor Necrosis Factor Inhibitors: Results Through One Year of a Phase 3b, Randomized, Controlled Study (COSMOS). Annals of the Rheumatic Diseases. November 2021.
- Deodhar, A., et al. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomized, placebo-controlled phase 3 trial. The Lancet, 2020:395(10230), 1115–1125. https://doi.org/10.1016/s0140-6736(20)30265-8
- Mease, P., et al Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomized, placebo-controlled phase 3 trial. The Lancet, 2020:395(10230), 1126–1136. https://doi.org/10.1016/s0140-6736(20)30263-4
- McInnes, I., et al. Long-term Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19 Subunit of Interleukin-23, Through 2 Years: Results from a Phase 3, Randomized, Double-blind, Placebo-controlled Study Conducted in Biologic-naïve Patients with Active Psoriatic Arthritis. Arthritis & Rheumatology, November 2021.
- ClinicalTrials.gov. A Study of Guselkumab in Participants With Active Psoriatic Arthritis (APEX). Available at: https://clinicaltrials.gov/ct2/show/NCT04882098. Accessed January 2022.
- ClinicalTrials.gov. Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent (SOLSTICE). Available at: https://clinicaltrials.gov/ct2/show/NCT04936308. Accessed January 2022.
- Thompson Jr., Dennis. How the Psoriasis Area and Severity Index Works. Everyday Health. https://www.everydayhealth.com/psoriasis/living-with/how-the-pasi-index-works/
- Sharp van der Heijde Score | Rheumatology. Department of Medicine Division of Rheumatology. Accessed January 2022. http://rheumatology.usherbrooke.ca/?q=scoresharp
- Felson, D. T., & LaValley, M. P. The ACR20 and defining a threshold for response in rheumatic diseases: too much of a good thing. Arthritis Research & Therapy, 2014:16(1), 101. https://doi.org/10.1186/ar4428
- Ruyssen-Witrand, A., et al. Efficacy and safety of biologics in psoriatic arthritis: a systematic literature review and network meta-analysis. RMD Open, 2020:6(1), e001117. https://doi.org/10.1136/rmdopen-2019-001117
- Kawalec, P., et al. Comparative effectiveness of abatacept, apremilast, secukinumab and ustekinumab treatment of psoriatic arthritis: a systematic review and network meta-analysis. Rheumatology International, 2017:38(2), 189–201. https://doi.org/10.1007/s00296-017-3919-7
- McInnes, I., et al. Secukinumab for psoriatic arthritis: comparative effectiveness versus licensed biologics/apremilast: a network meta-analysis. Journal of Comparative Effectiveness Research, 2018:7(11), 1107–1123. https://doi.org/10.2217/cer-2018-0075
- Lu, C., et al. Comparative efficacy and safety of targeted DMARDs for active psoriatic arthritis during induction therapy: A systematic review and network meta-analysis. Seminars in Arthritis and Rheumatism, 2019:49(3), 381–388. https://doi.org/10.1016/j.semarthrit.2019.06.001
- Belasco, J., & Wei, N. Psoriatic Arthritis: What is Happening at the Joint? Rheumatology and Therapy, 2019: 6(3), 305–315. https://doi.org/10.1007/s40744-019-0159-1
- Donvito T. CreakyJoints: What Is Enthesitis? The Painful Arthritis Symptom You Should Know About. Available at: https://creakyjoints.org/symptoms/what-is-enthesitis/. Accessed October 2021.
- Donvito T. CreakyJoints: What Is Dactylitis? The ‘Sausage Finger’ Swelling You Should Know About. Available at: https://creakyjoints.org/symptoms/what-is-dactylitis/. Accessed October 2021.
- Haddad A and Zisman D. Comorbidities in Patients with Psoriatic Arthritis. Rambam Maimonides Med J. 2017;8(1):e0004.
- National Psoriasis Foundation. About Psoriatic Arthritis. Available at: https://www.psoriasis.org/about-psoriatic-arthritis/ Accessed January 2022.
- Husted, J. A., et al. Occurrence and correlates of fatigue in psoriatic arthritis. Annals of the Rheumatic Diseases, 2008:68(10), 1553–1558. https://doi.org/10.1136/ard.2008.098202
- Cassell, S., & Kavanaugh, A. Psoriatic arthritis: Pathogenesis and novel immunomodulatory approaches to treatment. Journal of Immune Based Therapies and Vaccines. 2005;3:6. https://jibtherapies.biomedcentral.com/articles/10.1186/1476-8518-3-6
- Benson, J. M., et al. Discovery and mechanism of ustekinumab. MAbs, 2011:3(6), 535–545. https://doi.org/10.4161/mabs.3.6.17815
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