Johnson and Johnson’s (J&J) TREMFYA (guselkumab) is a dual-acting IL-23i that blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23. Johnson & Johnson expects it to be one of its major growth drivers. TREMFYA received its initial approval in the United States in July 2017 to treat moderate-to-severe plaque psoriasis in adults. Later, in July 2020, it gained approval for the treatment of active psoriatic arthritis in adults as well. 

1. Guselkumab’s Long-lasting Pain Relief in Psoriatic Arthritis Patients with TNFi Inadequate Response: COSMOS Phase IIIb Trial  (Abstract #POS0943)

Among patients randomized to guselkumab and placebo in COSMOS trial (NCT03796858), baseline values for pain visual analog scale (VAS), bodily pain, and tender joint count (TJC) were 64.6/60.3, 34.9/35.9, and 21.0/18.2, respectively. Guselkumab showed greater reductions in scores compared to placebo by Week 4, reaching statistical significance by week 8 for TJC, week 12 for pain VAS, and week 16 for bodily pain.

Kaplan-Meier analyses demonstrated meaningful pain improvement (≥15 mm and ≥30% improvement in pain VAS) with guselkumab compared to placebo from the first assessment at Week 4. The median time to achieve ≥15 mm, ≥20%, and ≥30% improvement in pain VAS with guselkumab was 8, 8, and 12 weeks, respectively. Cox regression analysis confirmed these findings.

At Weeks 24 and 48, response rates for ≥15 mm, ≥30%, and ≥50% improvement in pain VAS were higher with guselkumab compared to placebo. Among patients who achieved improvement at Week 24, a high percentage maintained their response at Week 48.

2. Assessment of Novel Psoriatic Arthritis 5-Thermometer Scale (PsA-5Ts) Domains During Guselkumab Treatment: Pooled Analysis of Three Phase III Trials (Abstract #POS0983)

Individuals with active PsA in COSMOS (NCT03796858), DISCOVER-1 (NCT03162796), and DISCOVER-2 (NCT03158285) were randomized to receive placebo, Guselkumab 100 mg at W0, W4, Q8W (every 8 weeks), or Q4W (every 4 weeks [DISCOVER-1/DISCOVER-2 only]). Changes in PsA-5T-Ds scores up to Week 24 were strongly correlated with variations in PASDAS (r=0.7) and moderately correlated with variations in DAPSA, cDAPSA, and SF-36 PCS (r=0.5). Achieving clinically meaningful improvement (CMI) through Week 24 in PASDAS, DAPSA, cDAPSA, and SF-36 PCS was associated with significantly greater improvement in PsA-5T-Ds scores compared to non-achievement. The cutoff for CMI in PsA-5T-Ds score was ≥8 points.

Treatment with guselkumab every 4 weeks or every 8 weeks resulted in significantly greater improvement in PsA-5T-Ds scores through Week 24 and higher odds of achieving PsA-5T-Ds CMI compared to placebo, after adjusting for potential confounders, starting from the first assessment time point.

KOL Insight:

“Early separation in pain response between patients treated with #guselkumab versus placebo. A significantly higher proportion of patients randomised to GUS reported meaningful improvements in pain by Week 8, and response rates for pain VAS endpoints in these patients increased through Week 48.” - Rheumatologist, UK

Conclusion: 

In real-world settings, TREMFYA demonstrated effectiveness and safety in managing PsA symptoms, showing a similar ACR response to various targeted PsA treatments such as SKYRIZI (risankizumab-rzaa) and RINVOQ (upadacitinib). Regarding PASI scores, TREMFYA performed better than many targeted PsA treatments, especially RINVOQ, and showed comparable efficacy to SKYRIZI. Sonelokimab and Izokibep inhibiting IL-17A, F, and IL-17A, respectively, are in an emerging pipeline of PsA and will give stiff competition to TREMFYA after approval. 

TREMFYA is being positioned as the USD 10.8 billion annual blockbuster STELARA's successor.  TREMFYA made around USD 3.14 billion in revenue globally in 2023. TREMFYA is anticipated to continue growing after obtaining near-term approval in a number of indications such as ulcerative colitis, and Crohn's disease.