Efficacy of Brodalumab and Guselkumab in Patients with Moderate-to-Severe Plaque Psoriasis Who are Inadequate Responders to Ustekinumab: A Matching Adjusted Indirect Comparison

Introduction Despite improved treatment options for plaque psoriasis within the last decades, some patients still have an inadequate response to treatment. Direct clinical evaluation between therapies used after biologic failure could facilitate physicians’ choice of treatment. Methods COBRA (NCT04533737) was a randomized (1:1), blinded (patient and assessor), 28-week, active-comparator trial conducted in Europe from December 2020 to December 2022. The objective was to compare the efficacy and safety of brodalumab versus guselkumab in adults with moderate-to-severe plaque psoriasis and inadequate response to ustekinumab. Patients received either brodalumab 210 mg or guselkumab 100 mg. The primary [having Psoriasis Area and Severity Index (PASI)-100 response at week 16] and key secondary (time to PASI-100 response) endpoints were tested in a fixed sequence. Results Due to delays and enrollment challenges, recruitment was terminated with 113 patients enrolled of 240 planned. The proportion of patients having PASI-100 at week 16 for brodalumab was 53.4% compared with 35.9% for guselkumab [odds ratio (OR) 2.05; 95% confidence interval (CI) 0.95, 4.44; p = 0.069]. As this was not statistically significant, the hierarchical testing procedure was stopped. All other secondary PASI endpoints had nominal p -values below 0.05 in favor of brodalumab. In the time to PASI response analyses, brodalumab separated from guselkumab in estimated cumulative incidence of patients achieving a response from week 2 onward, suggesting fast onset of action with brodalumab. Quality of life measures improved in both treatment groups. The safety findings were consistent with the known safety profiles. Conclusions Brodalumab showed a tendency toward better and earlier effect than guselkumab in patients who had failed ustekinumab. Thus, this trial provides important information in assisting physicians in their choice of therapy for patients who have failed their prior anti-interleukin (IL)-12/23 treatment. Trial Registration ClinicalTrials.gov identifier NCT04533737. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-023-01092-x.

Section: Discussionmentioning

confidence: 64%

Brodalumab Versus Guselkumab in Patients with Moderate-to-Severe Psoriasis with an Inadequate Response to Ustekinumab: A Randomized, Multicenter, Double-Blind Phase 4 Trial (COBRA)

Reich,

Bianchi,

Khemis

et al. 2024

“…MAIC approaches have been used in multiple disease areas [ 11 ], including a number of studies of treatments in dermatological indications. These include several comparisons of biological therapies for psoriasis [ 22 – 24 ], as well as a comparison of dupilumab and lebrikizumab monotherapy for AD [ 25 ]. The strength of the MAIC approach has recently been demonstrated in a study by Signorovitch et al [ 26 ], in which the results of two MAIC analyses of psoriasis therapies were compared with those of subsequently conducted RCTs of the same pairs of therapies [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Matching-Adjusted Indirect Comparison of the Efficacy at Week 32 of Tralokinumab and Dupilumab in the Treatment of Moderate-to-Severe Atopic Dermatitis

Torres,

Sohrt Petersen,

Ivens

et al. 2024

Introduction Tralokinumab and dupilumab are biological agents licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients who are candidates for systemic treatment. However, no head-to-head studies of their efficacy have been conducted. This study indirectly compared the efficacy of tralokinumab and dupilumab, both in combination with topical corticosteroids (TCS), at week 32. Methods An unanchored matching-adjusted indirect comparison was conducted using individual patient data (IPD) from the ECZTRA 3 tralokinumab trial and aggregate data from the LIBERTY AD CHRONOS dupilumab trial. IPD were selected by applying inclusion criteria from LIBERTY AD CHRONOS and weighting to match summary baseline characteristics—age, sex, race, body mass index, disease duration, Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and SCORing Atopic Dermatitis index—of patients treated with dupilumab. Week 32 outcomes of interest were 50%, 75% or 90% improvements in EASI (EASI-50, EASI-75 and EASI-90), IGA scores of 0 or 1 (IGA 0/1), ≥ 4-point improvement in worst daily pruritus numerical rating scale (NRS) score, and mean improvements in DLQI and the Patient Oriented Eczema Measure (POEM). Results After matching, tralokinumab and dupilumab, both in combination with TCS, showed similar efficacy across clinical response endpoints at week 32 (IGA 0/1, tralokinumab 49.9% vs dupilumab 39.3%; EASI-50, 78.9% vs 77.5%; EASI-75, 71.5% vs 71.9%; EASI-90, 53.3% vs 56.2%). The mean change from baseline in DLQI was statistically significantly larger in the matched tralokinumab plus TCS population than in the dupilumab plus TCS arm (− 12.1 vs − 10.4, p = 0.005). Changes in POEM and worst daily pruritus NRS were similar in the two groups. Conclusion The results of this analysis demonstrate that, in combination with TCS, tralokinumab and dupilumab have similar efficacy in the treatment of moderate-to-severe AD at 32 weeks of therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-024-01143-x.

“…One strength of the MAIC approach is that, as in the present study, it can be used to compare therapies for which no common comparator is available by aligning the mean characteristics of the populations [ 14 , 15 ]. In addition to the previous analysis comparing 4 weeks of Cal/BD foam therapy with 8 weeks of HP/Taz lotion [ 16 ], MAIC approaches have recently been used to compare Cal/BD foam to nonbiological systemic treatments for plaque psoriasis [ 19 ], as well as to compare the biological therapies brodalumab and guselkumab [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Matching-Adjusted Indirect Comparison of Long-Term Efficacy and Safety Outcomes for Calcipotriol Plus Betamethasone Dipropionate Foam Versus Halobetasol Proprionate Plus Tazarotene Lotion in the Treatment of Plaque Psoriasis

Adam

Bernasconi

Thoning

et al. 2022

Introduction: To date, there have been no head-to-head clinical studies comparing calcipotriol 0.005% plus betamethasone dipropionate 0.064% (Cal/BD) aerosol foam and halobetasol propionate 0.01% plus tazarotene 0.045% (HP/Taz) lotion for the treatment of plaque psoriasis. However, the efficacy of 4 weeks of Cal/BD foam and 8 weeks of HP/Taz lotion has been compared using a matchingadjusted indirect comparison (MAIC) approach. Here, we compare the efficacy and safety of Cal/ BD foam and HP/Taz lotion for up to 52 weeks. Methods: An unanchored MAIC was conducted using individual patient data from the PSO-LONG Cal/BD foam trial and a 52-week, openlabel phase 3 study of HP/Taz lotion (NCT02462083). Key outcomes of interest were Physician's Global Assessment (PGA) success (PGA 0/1 with C 2-point improvement) after 4 or 8 weeks of open-label therapy; the proportion of patients who had body surface area affected (BSA) B 3 after open-label therapy who maintained BSA B 3 to week 52; and adverse events (AEs).Results: After matching, patients were statistically significantly more likely to have PGA success after 4 weeks of Cal/BD foam than after 8 weeks of HP/Taz lotion (84.5% versus 54.4%; p \ 0.01). At week 52, 92.5% and 92.4% of patients receiving proactive and reactive Cal/BD foam, respectively, maintained BSA B 3, compared with 49.3% of those treated with HP/Taz lotion (both p \ 0.01). Treatment-related AEs, AEs leading to withdrawal, and AEs associated with drug application (dermatitis, application site pain, and pruritus) were significantly rarer with Cal/BD foam than with HP/Taz lotion (all p \ 0.01). Conclusions: Cal/BD aerosol foam demonstrated significantly greater efficacy than HP/ Taz lotion, and had a more favorable safety profile, compared with HP/Taz lotion, for up to 52 weeks. Proactive Cal/BD foam maintenance therapy and reactive use of Cal/BD foam