Biologics for psoriasis: towards oral therapies and less frequent dosing

Biological therapies have made tremendous progress for patients with psoriasis with many products now available. At IFPA 2024, Prof. Bruce Strober (Yale University, CT, USA) presented recent data on biologics, including long-term safety and efficacy, longer dosing intervals and oral therapies [1].

A recent large data set showed that bimekizumab is effective in scalp psoriasis. An analysis of 5 phase 3 trials showed that 84–88% of participants with plaque psoriasis receiving bimekizumab achieved scalp Investigator’s Global Assessment (IGA) of 0 depending on the dose regimen [2]. Furthermore, a pooled analysis of the same 5 trials showed that oral candidiasis occurs at decreasing yearly rates, inflammatory bowel disease was rare, and no active tuberculosis events were reported over 4 years of therapy [3].

Another recent long-term phase 3 study was LIMMItless (NCT03047395), investigating risankizumab versus placebo [4]. At 6 years, 86–87% of participants achieved ≥90% improvement in Psoriasis Area and Severity Index (PASI90), with participants achieving response by week 52 generally maintaining it durably. In terms of safety, no active tuberculosis or systemic candidiasis was reported and only 1 case of ulcerative colitis (<0.1% of participants).

The multipart GUIDE trial (NCT03818035) is assessing guselkumab treatment in patients with a short disease duration of psoriasis (<2 years) [5]. Part 3 of the trial assesses withdrawal of guselkumab 100 mg every 8 weeks or every 16 weeks treatment in patients who were initially ‘super-responders’ (PASI score 0) and who maintained PASI scores of <3. Following guselkumab treatment withdrawal, patients with ultra-short disease duration (<15 months) maintained their response much longer than patients with longer disease duration (median 450 days vs 291 days; P<0.0001).

JNJ-77242113 is a novel, small peptide, oral IL-23 receptor antagonist. This agent was assessed in the dose-ranging, randomised, phase 2 FRONTIER 1 trial (NCT05223868) in patients with PASI scores of ≥12 [6]. All assessed dose groups significantly improved disease activity compared with placebo. The 100 mg twice daily dose group of JNJ-77242113 led to significantly higher proportions of patients achieving PASI75 versus placebo at week 16 (78.6% vs 9.3%; P<0.001), as well as proportions of patients with PASI90 (59.5% vs 2.3%; P<0.001) and PASI100 (40.5% vs 0%; P<0.001). “This is probably the best response we’ve had with an oral formulation,” said Prof. Strober. Adverse events more commonly reported with JNJ-77242113 included nasopharyngitis, diarrhoea, and cough. Furthermore, a similar dose-ranging study FRONTIER 2 (NCT05364554) showed that 76.2% of patients receiving JNJ-77242113 100 mg twice daily achieved PASI75 at week 52, demonstrating maintenance of response with longer treatment [7].

Prof. Strober concluded that earlier intervention in patients with lower body surface area can offer long durations of therapy for responders. “It’s probably better to start intervening earlier because the therapies are relatively safe now,” said Prof. Strober. “I think in the next 3 to 5 years we will be dosing biologics 6 to 12 months with the same efficacy as we see with the current products.” Finally, we will also see “better orals or oral biologics for patients who demand oral therapies.”

1. 
   
   1. Strober BE. Psoriasis: Treatment advances in biologics. IFPA Conference 2024, 27–29 June, Stockholm, Sweden.
   2. Merola JF, et al. Abstract 4288, EADV Congress 2023, 11–14 October, Berlin, Germany.
   3. Gordon KB, et al. Poster 52671, 2024 AAD Annual Meeting, 8–12 March, San Diego, USA.
   4. Papp KA, et al. Poster 53833, 2024 AAD Annual Meeting, 8–12 March, San Diego, USA.
   5. Schäkel K, et al. Poster 50236, 2024 AAD Annual Meeting, 8–12 March, San Diego, USA.
   6. Bissonnette R, et al. FC08, EADV Congress 2023, 11–14 October, Berlin, Germany.
   7. Ferris LK, et al. Abstract S026, 2024 AAD Annual Meeting, 8–12 March, San Diego, USA.

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Posted on 17 July 202417 July 2024