Trial Results Show Efficacy of Extended Dosing Tremfya in Clearance of Psoriasis

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Findings from the Phase IIIb GUIDE clinical trial (NCT03818035) show that after early and complete clearance of psoriasis was achieved through treatment with Tremfya (guselkumab), disease control was maintained over an extended dosing interval of every 16 weeks, which showed noninferiorty to dosing every eight weeks.^1,2 Tremfya was the first FDA-approved, fully-human, dual-acting monoclonal antibody to block interleukin (IL)-23—a significant driver of the pathogenesis of inflammatory diseases—by attaching to the p19 subunit of IL-23 and to CD64, a receptor on cells that produce IL-23.

“The GUIDE trial, to our knowledge, is the first randomized clinical trial providing evidence that [Tremfya]-treated patients with early and complete skin clearance can maintain control of psoriasis with an extended dosing interval,” the study authors. “We demonstrated that [Tremfya] dosing every 16 weeks was noninferior to the standard every 8 weeks dosing interval for maintenance of disease control at [week] 68 in SRes, meeting the primary end point. Of note, disease control in the GUIDE trial was defined as [Psoriasis Area and Severity Index (PASI)] lower than 3, similar to treat-to-target goals proposed by national treatment guidelines.”¹

Tremfya has previously been approved by the FDA to treat adults with active psoriatic arthritis and for adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. A post-hoc analysis of the Phase III VOYAGE 2 (NCT02207244) clinical trial found Tremfya was associated with greater treatment persistence compared with Taltz (ixekizumab) or Cosentyx (secukinumab) in bio-experienced and bio-naïve patients with moderate-to-severe plaque psoriasis, showing durable clinical efficacy, itch relief, and quality-of-life improvements.³

The ongoing, double-blinded, parallel-group, multicenter GUIDE trial was conducted across 80 centers in Germany and France, enrolling adults with moderate to severe plaque psoriasis.

The three-part trial analyzed the impact of early disease intervention, prolonged dosing interval, and maintenance of response after treatment withdrawal. For part one, patients were administered Tremfya at a dose of 100 mg at weeks zero, four, 12, and 20. Patients achieving a PASI of 0 at weeks 20 and 28 were deemed super responders (SRes).

For part two of the trial, from weeks 28 to 68, SRes were randomly assigned to receive Tremfya at a dose of 100 mg every eight weeks or every 16 weeks, with non-SRes continuing on open-label Tremfya every eight weeks. The trial’s primary objective was demonstration of noninferiority with a 10% margin with Tremfya dosed every 16 weeks compared with every eight weeks among SRes in maintaining disease control with PASI <3 at week 68.

A total of 822 patients were administered Tremfya in part two of the trial (297 [36.1%] SRes [every 8 weeks/every 16 weeks; n = 148/n = 149] and 525 [63.9%] non-SRes). The trial achieved the primary endpoint of noninferiority with every 16 weeks dosing of Tremfya compared to every 8 weeks in SRes (P = .001), as 91.9% (137/149; 90% CI, 87.3%-95.3%) of SRes in the every 16 weeks dosing cohort and 92.6% (137/148; 90% CI, 88.0%-95.8%) of SRes in the every eight weeks dosing cohort achieved a PASI score lower than three at week 68. Additionally, the drug was well tolerated with no new safety signals reported.

“Our current findings suggest that early intervention with [Tremfya] increases the likelihood of achieving super response, and thus subsequently may be important to accommodate therapeutic strategies through dosing interval flexibility,” the study authors concluded. “The GUIDE clinical trial contributes critical prospective data to help address individual patient needs in everyday practice, and potentially improve long-term disease management and patient compliance with treatment.”¹

References

1. Eyerich K, Asadullah K, Pinter A, et al. Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis: The GUIDE Randomized Clinical Trial. JAMA Dermatol. Published online July 31, 2024. doi:10.1001/jamadermatol.2024.2463

2. A Study to Evaluate Further Therapeutic Strategies With Guselkumab in Participants With Moderate-to-Severe Plaque-Type Psoriasis (GUIDE). ClinicalTrials.gov. July 25, 2024. Accessed August 6, 2024. https://clinicaltrials.gov/study/NCT03818035

3. Tremfya (guselkumab) real-world data analyses show greater treatment persistence than IL-17s in both bio-naïve and bio-experienced patients living with moderate to severe plaque psoriasis. News release. Johnson & Johnson. March 17, 2023. Accessed August 6, 2024. https://www.jnj.com/tremfya-guselkumab-real-world-data-analyses-show-greater-treatment-persistence-than-il-17s-in-both-bio-naive-and-bio-experienced-patients-living-with-moderate-to-severe-plaque-psoriasis