Efficacy of secukinumab and adalimumab in patients with psoriatic arthritis and concomitant moderate-to-severe plaque psoriasis: results from EXCEED, a randomized, double-blind head-to-head monotherapy study

Abstract

Background: Secukinumab [an interleukin (IL)-17A inhibitor] has demonstrated significantly higher efficacy vs. etanercept (a tumour necrosis factor inhibitor) and ustekinumab (an IL-12/23 inhibitor) in patients with moderate-to-severe plaque psoriasis.

Objectives: To report 52-week results from a prespecified analysis of patients with active psoriatic arthritis (PsA) having concomitant moderate-to-severe plaque psoriasis from the head-to-head EXCEED monotherapy study comparing secukinumab with adalimumab.

Methods: Patients were randomized to receive secukinumab 300 mg via subcutaneous injection at baseline, week 1-4, and then every 4 weeks until week 48 or adalimumab 40 mg via subcutaneous injection every 2 weeks from baseline until week 50. Assessments in patients with concomitant moderate-to-severe psoriasis, defined as having affected body surface area > 10% or Psoriasis Area and Severity Index (PASI) ≥ 10 at baseline, included musculoskeletal, skin and quality-of-life outcomes. Missing data were handled using multiple imputation.

Results: Of the 853 patients [secukinumab (N = 426), adalimumab (N = 427)], 211 (24·7%) had concomitant moderate-to-severe psoriasis [secukinumab (N = 110, 25·8%), adalimumab (N = 101, 23·7%)]. Up to week 50, 5·5% of patients discontinued secukinumab vs.17·8% in the adalimumab group. The proportion of patients who achieved American College of Rheumatology (ACR) 20 response was 76·4% with secukinumab vs. 68·3% with adalimumab (P = 0·175), PASI 100 response was 39·1% vs. 23·8% (P = 0·013), and simultaneous improvement in ACR 50 and PASI 100 response at week 52 was 28·2% vs. 17·7%, respectively (P = 0·06). Secukinumab demonstrated consistently higher responses vs. adalimumab across skin endpoints.

Conclusions: This prespecified analysis in PsA patients with concomitant moderate-to-severe plaque psoriasis in the EXCEED study provides further evidence that IL-17 inhibitors offer a comprehensive biological treatment to manage the concomitant features of psoriasis and PsA.

Figure 1

Patient study treatment disposition up to week 52 in the psoriasis subset of patients with psoriatic arthritis. N, number of randomized patients; n, number of available patients; BSA body surface area; PASI, Psoriasis Area and Severity Index.

Figure 2

Kaplan–Meier time to study treatment discontinuation curve in the psoriasis subset of patients with psoriatic arthritis. ADA, adalimumab; SEC, secukinumab. P‐value vs. adalimumab. Numbers of patients at risk are presented for SEC and ADA.

Figure 3

ACR 20/50, PASI 90 response rates, resolution of enthesitis, mean change from baseline in HAQ‐DI through week 52 in the psoriasis subset of patients with psoriatic arthritis. N, number of active PsApatients who had body surface area (BSA) > 10% or PASI ≥ 10 affected by psoriasis at baseline. ACR, American College of Rheumatology; csDMARD, conventional synthetic disease modifyinganti‐rheumatic drugs; HAQ‐DI, health assessment questionnaire‐disability index; PASI, psoriasis area severity index; PsA, psoriatic arthritis. P‐value vs. adalimumab. Unadjusted P‐values are reported at week 52. Binary outcomes (ACR 20, PASI 90, ACR 50 and resolution of enthesitis) were assessed using logistic regression; mean change from baseline in HAQ‐DI was analysed using a mixed‐effect model with repeated measures and HAQ‐DI was analysed using logistic regression. Patients who discontinued study treatment before or at week 50 or took csDMARDs after week 36 are considered nonresponders for the visits after discontinuation or taking csDMARDs. Multiple imputation is used for all other missing data.

Figure 4

Combined ACR 50 + PASI 100 response rate through week 52 in the psoriasis subset of patients with psoriatic arthritis. N, number of active PsA patients who had body surface area (BSA) > 10% or PASI ≥ 10 affected by psoriasis at baseline. ACR, American College of Rheumatology; csDMARD, conventional synthetic disease modifyinganti‐rheumatic drugs; PASI, psoriasis area severity index; PsA, psoriatic arthritis. P‐value vs. adalimumab. Unadjusted P‐values are reported at week 52. Patients who discontinued study treatment before or at week 50 or took csDMARDs after week 36 are considered nonresponders for the visits after discontinuation or taking csDMARDs. Multiple imputation is used for all other missing data.

Figure 5

PASI 100 and PASI 75 response rates and mean change from baseline in DLQI and DLQI 0/1 response through week 52 in the psoriasis subset of patients with psoriatic arthritis. N, number of active PsA patients who had body surface area (BSA) > 10% or PASI ≥ 10 affected by psoriasis at baseline. csDMARD, conventional synthetic disease modifying anti‐rheumatic drugs; DLQI, dermatology life quality index; PASI, Psoriasis Area Severity Index; PsA, psoriatic arthritis. P‐value vs. adalimumab. Unadjusted P‐values are reported at week 52. Patients who discontinued study treatment before or at week 50 or took (csDMARDs) after week 36 are considered nonresponders for the visits after discontinuation or taking csDMARDs. Multiple imputation is used for all other missing data. A mixed‐effect model with repeated measures was used to assess mean change from baseline in DLQI.