Extension of ustekinumab maintenance dosing interval in moderate-to-severe psoriasis: results of a phase IIIb, randomized, double-blinded, active-controlled, multicentre study (PSTELLAR)

Abstract

SummaryBackground Phase III studies showed that some patients maintained response for ≥ 6 months following ustekinumab discontinuation. Objectives To assess clinical responses with extended ustekinumab maintenance dosing intervals. Methods Adults with moderate-to-severe plaque psoriasis received ustekinumab at weeks 0, 4 and 16 during open-label treatment. Patients achieving a week-28 Physician's Global Assessment (PGA) score of cleared/minimal (PGA = 0/1) were randomized 1 : 4 to group 1 [approved every 12 weeks (q12 wk) maintenance] or group 2 (q12-24 wk; response-based dosing determined by time to loss of PGA = 0/1). Key end points included the number of visits with PGA = 0/1 (primary end point) and ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) between weeks 88 and 112, and PGA/PASI responses between weeks 28 and 112. Results Overall, 378 patients achieved PGA = 0/1 at week 28 and were randomized to group 1 (n = 76) or group 2 (n = 302). Patients in group 1 had numerically greater mean numbers of visits with PGA = 0/1 than group 2 and also with PASI 75 from week 88 to 112. A higher proportion of patients in group 1 (55%) than group 2 (39%) had PGA = 0/1 at all seven visits from week 88 to 112. Maintenance of response was observed with dose-interval extension beyond q12 wk in a subset of patients. Extending the dosing interval did not affect antibody development or safety. Conclusions Efficacy was better maintained among week-28 PGA responders randomized to continue q12 wk ustekinumab vs. extending maintenance dosing based on clinical response, although some patients maintained high levels of efficacy with up to q24 wk dosing.

Targeted therapies for patients with moderate-to-severe psoriasis: a systematic review and network meta-analysis of PASI response at 1 year

“…Sixteen studies were excluded from the NMA due to differences in study design and the comparisons made. This included data from nine responderenriched randomized withdrawal maintenance phase studies (23)(24)(25)(26)(27)(28)(29)(30)(31) and one responder-enriched re-randomized dose comparison study of tildrakizumab (32). Three studies comparing different doses or dosing regimens of comparators listed in the eligibility criteria were excluded (33)(34)(35) as was a study comparing a biosimilar etanercept to the originator product (36).…”

Using Real‐World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic‐Pharmacodynamic Study

“…On the other hand, a recent phase IIIb study reports a subset of patients in who complete response was maintained, despite lengthening the dosing interval. 22 Psoriasis represents an ideal disease model to investigate the utility of TDM, 6,23 because treatment response is visually observed and easily quantifiable over time. Here, we use a large-scale real-world data set from the multicenter cohort study Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP), within the UK pharmacovigilance registry British Association of Dermatologists Biologics and Immunomodulators Registry (BADBIR).…”

“…Real‐world data show that those with higher baseline body mass index are less likely to respond, and more likely to need higher cumulative doses over the first year of treatment, suggesting that a proportion of patients may have insufficient drug exposure. On the other hand, a recent phase IIIb study reports a subset of patients in who complete response was maintained, despite lengthening the dosing interval …”

Safety of guselkumab in patients with moderate‐to‐severe psoriasis treated through 100 weeks: a pooled analysis from the randomized VOYAGE 1 and VOYAGE 2 studies

“…Additionally, when biological treatment was administered on an ‘as needed’ basis [i.e. only when patients do not maintain response thresholds such as ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) or Physician's Global Assessment score of 0/1], results have been inferior to those achieved with regularly administered therapy …”