Adjusted treatment COMPArisons between guSelkumab and uStekinumab for treatment of moderate-to-severe plaque psoriasis: the COMPASS analysis

Abstract

Background: Guselkumab is an interleukin-23 inhibitor indicated for the treatment of moderate-to-severe plaque psoriasis in adults. Guselkumab has demonstrated additional benefit in patients with early inadequate response to ustekinumab. Long-term efficacy comparisons of guselkumab and ustekinumab are currently lacking among ustekinumab-naive patients.

Objectives: To assess the relative efficacy of guselkumab and ustekinumab for maintenance therapy of moderate-to-severe plaque psoriasis, using individual patient data (IPD) from randomized controlled trials.

Methods: IPD for guselkumab from the VOYAGE 1 and 2 trials were pooled and compared with IPD for ustekinumab from the NAVIGATE trial. Multivariable logistic regression analyses compared guselkumab 100 mg and ustekinumab 45 mg or 90 mg for the achievement and maintenance of Psoriasis Area and Severity Index (PASI) 90, 75 and 100 responses up to 40 weeks. The regression models accounted for a range of clinically relevant covariates (e.g. age, sex, psoriasis duration). Relative efficacy was expressed using odds ratios (ORs) and predicted probability of treatment response associated with each intervention.

Results: Patients receiving guselkumab had significantly higher probabilities of achieving a PASI 90 response than patients receiving ustekinumab, at both week 16 [70·4% vs. 46·0%, OR 2·79, 95% confidence interval (CI) 2·22-3·45] and week 40 (74·2% vs. 54·5%, OR 2·40, 95% CI 1·89-3·13]. Guselkumab was also associated with a significantly increased likelihood of achieving both PASI 75 and PASI 100 responses at weeks 16 and 40, compared with ustekinumab.

Conclusions: Adjusted analyses leveraging IPD demonstrate that guselkumab has a significantly higher probability of achieving and maintaining PASI treatment responses through week 40 than ustekinumab does.

Figure 1

Overview of study designs and approach to adjustments for crossovers in the VOYAGE 2 and NAVIGATE studies. (a) NAVIGATE. As nonresponding patients were randomly assigned to continue ustekinumab vs. switching to guselkumab, patients in both arms can be considered exchangeable, and outcomes for the nonresponding ustekinumab patients who continued on ustekinumab after randomization can be considered to constitute a valid counterfactual for the patients randomized to guselkumab. To estimate unbiased outcomes for the entire cohort and eliminate the impact of treatment switching at week 16, nonresponders who continued with ustekinumab were upweighted to represent the outcome for the patients switched to guselkumab as if they had continued ustekinumab. (b) VOYAGE 1. No adjustments for crossovers needed. (c) A similar approach as described for NAVIGATE was applied to VOYAGE 2 to deal with rerandomization of responding patients in the guselkumab arm at week 28 data. IGA, Investigator's Global Assessment; R, randomized; UST, ustekinumab; W, week.

Figure 2

Hierarchy of evidence for comparing interventions; adapted from Coyle et al.26 AD, aggregated data; IPD, individual patient data; ITC, indirect treatment comparison; ITT, intention to treat; MAIC, matching‐adjusted indirect comparison; NMA, network meta‐analysis; RCT, randomized controlled trial.

Figure 3

Estimated covariate effects from logistic regression, Psoriasis Area and Severity Index 90 response at week 40. Treatment and covariate effects were estimated using multivariable logistic regression and are expressed as odds ratios with corresponding 95% confidence intervals. BSA, body surface area; IGA, Investigator's Global Assessment; LCL, lower 95% confidence limit; OR, odds ratio; PASI, Psoriasis Area and Severity Index; PS, psoriatic; PSO, psoriasis; UCL, upper 95% confidence limit; ^areference value.

Figure 4

Predicted rates of a Psoriasis Area and Severity Index 90 treatment response for guselkumab and ustekinumab, based on data from the VOYAGE, NAVIGATE and PHOENIX trials, with 95% confidence intervals. Predicted rates were derived from the multivariable logistic regression model, as described in the study methods. CI, confidence interval; GUS, guselkumab; PASI, Psoriasis Area and Severity Index; UST, ustekinumab.

Figure 5

Adjusted comparisons for guselkumab vs. ustekinumab: achievement of Psoriasis Area and Severity Index (PASI) 90, 75 and 100 responses at week 40. Odds ratios from multivariable logistic regression analyses comparing guselkumab and ustekinumab for PASI response outcomes at 40 weeks of follow‐up are shown. In both primary and secondary analyses, guselkumab was associated with a statistically significantly increased likelihood of treatment response. Predicted probabilities of response associated with each intervention are also provided for each outcome measure. CI, confidence interval.