J&J's Strategic Shift in Rheumatology and IL-23 Targeting Therapies: A New Era for PsA Treatment

Johnson & Johnson’s (J&J) strategic reallocation of R&D resources from interleukin-6 (IL-6) inhibition to interleukin-23 (IL-23) targeting therapies marks a pivotal shift in the biopharma landscape. This pivot, driven by evolving scientific insights and clinical outcomes, positions J&J as a leader in addressing unmet needs in psoriatic arthritis (PsA) through its flagship IL-23 inhibitor, TREMFYA® (guselkumab). While IL-6 inhibition remains a cornerstone for rheumatoid arthritis (RA), J&J’s focus on IL-23 reflects a calculated response to the limitations of earlier pathways and the growing evidence of IL-23’s role in PsA pathogenesis.

The IL-6 Inhibition Plateau

IL-6 inhibition, exemplified by tocilizumab, has long been a mainstay for RA, reducing inflammation and comorbidities like anemia and cardiovascular disease [1]. However, the efficacy of IL-6 inhibitors in PsA has been less compelling. Clinical trials for IL-6 blockers in PsA have shown mixed results, with some studies failing to demonstrate significant structural joint damage inhibition [2]. For instance, sirukumab, an IL-6 inhibitor, was terminated due to safety concerns, underscoring the pathway’s challenges [3]. These limitations, coupled with the heterogeneity of PsA, prompted J&J to redirect its efforts toward IL-23 inhibition—a cytokine increasingly recognized for its role in driving Th17-mediated inflammation in PsA.

TREMFYA’s Breakthrough in IL-23 Inhibition

J&J’s TREMFYA (guselkumab) has emerged as a game-changer in PsA treatment. The Phase 3b APEX study demonstrated that guselkumab significantly inhibited structural joint damage progression, with a mean change in the PsA modified van der Heijde-Sharp (vdH-S) score of 0.55 for patients receiving the drug every four weeks (Q4W) and 0.54 for those on an eight-week regimen (Q8W), compared to 1.35 in the placebo group [4]. Notably, 67% of Q4W and 63% of Q8W patients showed no radiographic progression, versus 53% in the placebo group [4]. These results, combined with improvements in joint and skin symptoms (67% and 68% achieving ACR20 response rates, respectively), have led J&J to submit a supplemental Biologics License Application (sBLA) to expand TREMFYA’s label to include structural damage inhibition [5].

The drug’s dual mechanism—blocking IL-23 and binding to CD64—offers a unique advantage over competitors. Unlike IL-6 inhibitors, which broadly suppress inflammation, IL-23 inhibition targets the root drivers of PsA, including Th17 cell differentiation and innate lymphoid cell activation [6]. This precision has translated into superior long-term outcomes, with TREMFYA now the first and only IL-23 inhibitor proven to halt structural joint damage in PsA [7].

Strategic Reallocation and Market Implications

J&J’s shift from IL-6 to IL-23 inhibition reflects a broader industry trend toward pathway-specific therapies. While IL-6 inhibitors remain critical for RA, their role in PsA is limited by the disease’s distinct immunological profile. By contrast, IL-23 inhibition aligns with PsA’s complex interplay of skin, gut, and joint inflammation [8]. This strategic reallocation has not only strengthened J&J’s pipeline but also positioned it to capitalize on the growing PsA market, projected to exceed $10 billion by 2030.

Risks and Opportunities

Despite TREMFYA’s success, challenges persist. The Most-Favored-Nation pricing policy in the U.S. could pressure margins for high-cost biologics like TREMFYA [9]. Additionally, biosimilars for IL-6 inhibitors may erode RA market share, though PsA remains a growth area. J&J’s recent focus on FcRn-blocking therapies, such as nipocalimab for Sjögren’s Disease, further diversifies its immunology portfolio, mitigating risks from any single pathway [10].

Conclusion

J&J’s strategic pivot to IL-23 inhibition underscores its agility in navigating the evolving rheumatology landscape. TREMFYA’s structural damage inhibition in PsA represents a paradigm shift, offering investors a compelling case for long-term value. As the company continues to refine its IL-23 and TYK2 inhibition strategies, it is well-positioned to redefine treatment standards in PsA and beyond.

Source:
[1] What have we learnt from the inhibition of IL-6 in RA and identifying the clinical opportunities for patient outcomes? [https://pmc.ncbi.nlm.nih.gov/articles/PMC11497505/]
[2] Why Inhibition of IL-23 Lacked Efficacy in Ankylosing [https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.614255/full]
[3] Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis [https://pmc.ncbi.nlm.nih.gov/articles/PMC10789669/]
[4] New data show TREMFYA® (guselkumab) is the only IL-23 inhibitor proven to significantly inhibit progression of joint structural damage in active psoriatic arthritis [https://www.jnj.com/media-center/press-releases/new-data-show-tremfya-guselkumab-is-the-only-il-23-inhibitor-proven-to-significantly-inhibit-progression-of-joint-structural-damage-in-active-psoriatic-arthritis]
[5] Johnson & Johnson files with U.S. FDA to include new evidence in TREMFYA® (guselkumab) label as the only IL-23 inhibitor to demonstrate significant inhibition of joint structural damage in active psoriatic arthritis [https://www.jnj.com/media-center/press-releases/johnson-johnson-files-with-u-s-fda-to-include-new-evidence-in-tremfya-guselkumab-label-as-the-only-il-23-inhibitor-to-demonstrate-significant-inhibition-of-joint-structural-damage-in-active-psoriatic-arthritis]
[6] IL-23 and its role in linking inflammation of the skin, gut and ... [https://pmc.ncbi.nlm.nih.gov/articles/PMC8527243/]
[7] TREMFYA® (guselkumab) is the first and only IL-23 inhibitor to significantly reduce both the signs and symptoms and the progression of structural damage in adults living with active psoriatic arthritis [https://www.jnj.com/media-center/press-releases/tremfya-guselkumab-is-the-first-and-only-il-23-inhibitor-to-significantly-reduce-both-the-signs-and-symptoms-and-the-progression-of-structural-damage-in-adults-living-with-active-psoriatic-arthritis]
[8] 6 Rheumatology Headlines You Missed in July 2025 [https://www.hcplive.com/view/6-rheumatology-month-in-review-june-2025]
[9] Lowest Price, Highest Risk? New Drug Policy's Potential Effect on Rheumatology [https://www.the-rheumatologist.org/article/lowest-price-highest-risk-new-drug-policys-potential-effect-on-rheumatology/]
[10] Johnson & Johnson advances leadership in rheumatic disease innovation with 43 abstracts at ACR 2024 [https://www.jnj.com/media-center/press-releases/johnson-johnson-advances-leadership-in-rheumatic-disease-innovation-with-43-abstracts-at-acr-2024]