Tildrakizumab maintains treatment efficacy for moderate to severe psoriasis for 5 to 6 months when treatment is interrupted, according to study findings published in the Journal of the European Academy of Dermatology and Venereology. Higher risk for relapse was associated with increased body mass index (BMI), smoking, and longer disease duration.
Investigators conducted a posthoc analysis using data from a reSURFACE 1 phase 3 trial of 772 adult patients with moderate to severe plaque psoriasis treated with tildrakizumab, an interleukin-23 p-19 subunit (IL-23p19) blocker. The study’s primary outcome was time to relapse in tildrakizumab responders (at least 75% improvement in Psoriasis Area and Severity Index; PASI 75) who were re-randomly assigned to placebo from week 28 to week 64.
At week 0, 617 patients were randomly assigned to either tildrakizumab 100 or 200 mg. At week 28, the 438 PASI 75 responders were re-randomly assigned 1:1 in a double-blinded manner to continue the same tildrakizumab dose or receive a placebo until relapse, defined as a reduction in maximum PASI by 50%. Tildrakizumab doses were given at week 0, week 4, and every 12 weeks thereafter.
At week 64, the median time to relapse for tildrakizumab withdrawal patients was 20 to 25 weeks for tildrakizumab 100 and 200 mg patients, respectively (P = .2191), or 32 to 37 weeks from the last tildrakizumab dose. No relapse was seen in 20.2% and 24.4% of tildrakizumab 100 and 200 mg withdrawal patients, respectively, which was 48 weeks from the last dose. These patients either maintained a PASI 75 response (91.3% and 89.7% of tildrakizumab 100 and 200 mg withdrawal groups, respectively) or were lost to follow-up (8.7% and 10.3% of tildrakizumab 100 and 200 mg withdrawal groups, respectively). There was no statistically significant difference in the relapse rates between responders to tildrakizumab 100 and 200 mg.
According to a logistic regression model, patients who smoked were twice as likely to lose a PASI 75 response compared with non-smokers (odds ratio [OR], 2.039, 95% confidence interval [CI], 1.020 to 4.073, P = .0437). The odds of losing a PASI 75 response was 7% higher for every 1-unit increase in BMI (OR, 1.073, 95% CI, 1.016 to 1.132, P = .0115) and 3% higher for every 1-year increase in disease duration (OR, 1.033, 95% CI, 1.001 to 1.067, P = .0458). A Cox regression analysis confirmed that elevated BMI and longer disease duration were associated with an increased risk for relapse, with a 4% increased risk for every 1-unit increase in BMI (hazard ratio [HR], 1.035, 95% CI, 1.0112 to 1.0582, P = .0034) and a 2% increased risk for every 1-year increase in disease duration (HR, 1.0151, 95% CI, 1.0028 to 1.0275, P = .0155).
A limitation of the study was the lack of consensus regarding how to define psoriasis relapse, making comparisons in studies difficult.
The study highlights that IL-23p19 blockers are effective in delaying psoriasis relapse, the researchers believe, which is pertinent information for clinicians whose patients need to interrupt therapy. In addition, predictive factors of relapse such as BMI and smoking are modifiable, it was noted, and clinicians can address these areas with patients to reach better treatment outcomes.
Disclosure: Several study authors declared receiving grants and personal fees from the pharmaceutical industry. Please see the original reference for a full list of the authors’ disclosures.
Warren RB, Carrascosa JM, Fumero E, et. al. Time to relapse after tildrakizumab withdrawal in patients with moderate-to-severe psoriasis who were responders at week 28: post-hoc analysis through 64 weeks from resurface 1 trial. J Eur Acad Dermatol Venereol. Published online September 10, 2020. doi: 10.1111/jdv.16964