Phases IIa trial reports that tildrakizumab treatment did not improve ASAS20 response rate in ankylosing spondylitis patients

An anti-interleukin-23p19 monoclonal antibody known as tildrakizumab has received approval for treating moderate to severe plaque psoriasis. However, a recent study published in the Journal of Clinical Rheumatology has indicated that tildrakizumab is well-tolerated among patients with ankylosing spondylitis (AS), yet it did not achieve a 20% improvement from the baseline according to the Assessment on SpondyloArthritis International Society Criteria (ASAS20) by week 24. 

Dr. Eric Peters and his associates conducted the randomized, double-blind, placebo-controlled phase 2a study to evaluate the safety and efficacy of tildrakizumab in 101 active AS patients. At week 24, tildrakizumab 200 mg-treated patients had an ASAS20 response rate of 74.0%, while placebo-treated patients had an ASAS20 response rate of 80.4% (n=51; treatment difference, 6.31%; P=0.44). There was no apparent difference in treatment impact among subgroups. Thus, treatment with tildrakizumab was usually well tolerated, and no unexpected safety results were observed. Due to a lack of efficacy, the study was discontinued at the week 24 interim analysis. 

Results from a 2021 randomized, double-blind, placebo-controlled, multiple-dose, 52-week phase IIb study revealed improvements in joint and skin manifestations of patients with psoriatic arthritis following tildrakizumab treatment. At week 24, 71.4%-79.5% of patients receiving tildrakizumab, compared to 50.6% of those receiving a placebo, achieved the American College of Rheumatology criteria (ACR20) (all P <0.01). Those administered tildrakizumab experienced higher rates of ACR50, minimal disease activity, and improvements of 75%/90%/100% from baseline in the Psoriasis Area and Severity Index responses at week 24 and continuing through week 52, in contrast to the placebo group. Throughout the 52-week duration, treatment-emergent adverse events and significant treatment-emergent adverse events were seen in 64.5% and 3.3% of participants, respectively, and showed similar patterns across treatment groups. 

In conclusion, tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, holds significant promise in addressing moderate to severe plaque psoriasis. However, its application in managing AS has not yielded promising therapeutic results. Since the potential of tildrakizumab in AS treatment has not reached the desired outcome observed in psoriasis management, its broader implications in related conditions and specialized populations warrant further exploration. 

References 

  1. Peters E, Chou RC, Rozzo SJ, Yao SL, Fructuoso FJ. A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study of Tildrakizumab Efficacy and Safety in Patients With Active Ankylosing Spondylitis. JCR: Journal of Clinical Rheumatology. 2023 Aug 1;29(5):223-9. 
  2. Mease PJ, Chohan S, Fructuoso FJG, Luggen ME, Rahman P, Raychaudhuri SP, Chou RC, Mendelsohn AM, Rozzo SJ, Gottlieb A. Efficacy and safety of tildrakizumab in patients with active psoriatic arthritis: results of a randomised, double-blind, placebo-controlled, multiple-dose, 52-week phase IIb study. Ann Rheum Dis. 2021 Sep;80(9):1147-1157. 

 

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