Onset of Action of Antipsoriatic Drugs for Moderate-to-Severe Plaque Psoriasis: An Update

Psoriasis vulgaris is an inflammatory skin disease characterized by quickly thickening and scaling plaques affecting the skin and nails,¹ which can cause discomfort, pain, and social distress² for the 1 to 2 percent of the American population^3,4 and 2 to 3 percent of the global population^5,6 that suffer from the disease. The advent of new biologic therapies has improved the quality of life of patients with moderate-to-severe psoriasis,⁷ and rapid disease improvement has been rated to be among the most important attributes of treatment success.⁸ Two studies have reviewed the time for patients to achieve clinically meaningful improvements (TOA) measured by the Psoriasis Area and Severity Index (PASI) with various antipsoriatric drugs.^9,10 However, neither review is up-to-date with clinical data for certolizumab pegol and tildrakizumab.This review aims to synthesize data from previous TOA reviews for antipsoriatic drugs, update these analyses with clinical data of tildrakizumab and certolizumab pegol, and add recently published clinical data on apremilast and low-dose acitretin.

Identification of StudiesWe consolidated clinical data from recent publications and presentations of certolizumab pegol (CZP), tildrakizumab, apremilast, and low-dose acitretin as well as two previous TOA reviews. The first was a systematic review that identified trials performed according to the German S3 psoriasis guidelines^10,11  and grouped data on study arms where comparable dosages and outcome criteria were used and then reported weighted means by considering the number of patients in each study arm and assuming a linear course of PASI response between provided timepoints.¹⁰ An update to this review compared the TOA for these antipsoriatic drugs with clinical data for brodalumab, secukinumab, ustekinumab, and ixekizumab from individual studies or pooled data where TOA had already been calculated by linear interpolation or Kaplan-Meirer estimation.⁹ Clinical data from both these TOA reviews were combined with clinical data for CZP from CIMPASI-1 and CIMPASI-2¹² as well as CIMPACT¹³ trials obtained from UCB, clinical data for tildrakizumab from reSURFACE 1 and reSURFACE 2 trials¹⁴ obtained from Sun Pharma, and published data for apremilast¹⁵ and low-dose acitretin.¹⁶ In our analysis of clinical data not previously reviewed, we also assumed a linear course of the PASI response between the different measured time points in order to perform linear interpolation.¹⁰Primary and Secondary OutcomesThe primary outcome of our review was the time necessary for 25% of patients in a study population to achieve at least a Psoriasis Area and Severity Index (PASI) 75 response. The secondary outcome of our review was the time necessary for a study population to achieve a mean PASI 50 response. While there are more than 50 clinical measures that can be used to measure psoriasis severity such as DLQI (Dermatology Life Quality In