Guselkumab Outperforms Ustekinumab in Indirect Comparison PsA Analysis

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Individual patient-level data (IPD) analysis showed patients with psoriatic arthritis (PsA) receiving treatment with guselkumab were more likely to achieve American College of Rheumatology 20% improvement (ACR20) when compared with those treated with ustekinumab, according to a study published in Rheumatology and Therapy.¹ These results were superior from week 16 in biologic-naïve patients and week 24 in biologic-experience patients.

The Psoriasis Area Severity Index 90% reduction (PASI 90) response were observed at weeks 16 and 52 for both subgroups.

Although previous data have revealed guselkumab and ustekinumab, both fully human monoclonal antibodies, demonstrated superior efficacy when compared with placebo in clinical trials, no head-to-head trials have compared the safety and efficacy of these treatments. The indirect treatment comparison (ITC) methods determine comparative effectiveness when head-to-head randomized controlled trials (RCTs) are unavailable. Network meta-analyses (NMA) are used to compare multiple treatments both directly and indirectly using a common factor, such as placebo.²

‘There are methodological challenges with conducting NMAs assessing long-term comparative efficacy,” wrote lead investigator Pushpike Thilakarathne, PhD, statistician in the HEMAR Department at Janssen Pharmaceutica in Beerse, Belgium, and colleagues.

“A key reason for the lack of long-term NMAs is that trial designs typically include a planned cross-over to active treatment after an initial placebo-controlled period. This makes anchored analyses invalid and instead, methodologically appropriate analyses require a comparison of continuously treated active patients which is achieved by leveraging IPD from a treatment’s RCT.”

Investigators compared the 2 treatments on joint and skin efficacy up to week 52 using pooled IPD from the DISCOVER-1, DISCOVER-2, PSUMMIT-1, and PSUMMIT-2 trials. Baseline characteristics, PASI response, and ACR scores were collected. Multivariate logistic regression adjusted for any differences in patient characteristics across trials.

The baseline characteristics for patients treated with guselkumab (100 mg every 8 weeks [Q8W]; 100 mg every 4 weeks [Q4W]) were comparable to the ustekinumab cohort (45/90 mg).

In the biologic-naïve group, patients receiving guselkumab demonstrated significantly higher ACR20 20 (Q8W: 1.97; 1.37, 2.84; Q4W: 2.04; 1.40, 2.96) and PASI 90 (Q8W: 2.33; 1.52, 3.56; Q4W: 2.57; 1.67, 3.97) when compared with ustekinumab starting at week 16.

Similarly, for biologic-experienced patients, both guselkumab doses achieved significantly higher ACR20 (Q8W: 2.57; 1.11, 5.93; Q4W: 2.63; 1.12, 6.17) compared with ustekinumab starting at week 24. Both guselkumab doses were also superior to ustekinumab for PASI 90 at week 16 and 52 (Q8W: 3.96; 1.39, 11.27; Q4W: 13.10; 4.18, 41.04).

The efficacy of guselkumab was comparable and robust across the primary, scenario, and sensitivity analyses.

Investigators noted limitations including the validity of relative treatment effects from the unanchored ITCs as they relied on the assumption that the observable and unobservable prognostic factors were balanced. Additionally, there is a possibility some covariates which were not considered in the analysis could have impacted the outcomes of interest. Confounding factors and biases could have been unintentionally introduced as the studies were performed in different settings, different time periods, and different countries. To minimize this, investigators used certain clinically relevant patient characteristics.

“Leveraging IPD from phase 3 studies demonstrated that both guselkumab doses were generally more effective versus ustekinumab for joint and skin outcomes up to 52 weeks, consistently in both biologic-naïve and biologic-experienced groups,” investigators concluded. “Future studies are encouraged to assess long-term comparative efficacy beyond 52 weeks.”

References

1. ^{Thilakarathne P, Schubert A, Peterson S, Noel W, Patel BP, Hassan F. Comparing Efficacy of Guselkumab versus Ustekinumab in Patients with Psoriatic Arthritis: An Adjusted Comparison Using Individual Patient Data from the DISCOVER and PSUMMIT Trials. Rheumatol Ther. 2024;11(2):457-474. doi:10.1007/s40744-024-00644-7}
2. ^{Catala-Lopez F, Tobias A, Cameron C, Moher D, Hutton B. Network meta-analysis for comparing treatment effects of multiple interventions: an introduction. Rheumatol Int. 2014;34(11):1489–96.}