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

A.B. Gottlieb; J.F. Merola; K. Reich; F. Behrens; P. Nash; C.E.M. Griffiths; W. Bao; P. Pellet; L. Pricop; I.B. McInnes


The British Journal of Dermatology. 2021;185(6):1124-1134. 

In This Article

Abstract and Introduction


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.


Psoriasis is an immune-mediated inflammatory disease with a prevalence varying from 0·14% [95% confidence interval (CI) 0·05–0·4%] in East Asia to 1·92% in Western Europe (1·1–3·5%) in the adult population.[1] Psoriatic arthritis (PsA) is a heterogeneous chronic disease that can affect peripheral and axial joints, and entheses.[2] PsA and psoriasis have related but different pathogenic mechanisms, with shared and unshared genetic factors and environmental stimuli contributing to the disease incidence and severity of both conditions.[3] Approximately 30% of patients with psoriasis develop PsA, often subsequent to the onset of skin disease. Hence, dermatologists have the opportunity to detect PsA before the patients are referred to rheumatologists.[4]

Recent European League Against Rheumatism 2019 recommendations suggest that the primary goal of treating patients with PsA should be to maximize health-related quality of life (HRQoL), through control of symptoms, prevention of structural damage, normalization of function and social participation. When evaluating whether a therapy is effective in PsA, it is vital to understand the efficacy in the context of active psoriasis and whether the therapy improves symptoms specifically associated with PsA. Patients with psoriasis, PsA, or both, generally have reduced HRQoL and productivity.[5]

Many patients with PsA who have concomitant psoriasis and musculoskeletal symptoms show inadequate clinical responses or intolerance to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), including methotrexate (MTX), both in musculoskeletal and nonmusculoskeletal manifestations in patients with PsA.[6] Similar to PsA, recent treatment recommendations for psoriasis suggest initiating biological therapy for patients if MTX or ciclosporin have failed, or considering biological therapy earlier in the treatment plan if MTX is not well tolerated.[7]

Adalimumab, a human monoclonal antibody against tumour necrosis factor (TNF), is widely used as a first-line biological disease-modifying antirheumatic drug (bDMARD) in the treatment of patients with PsA, with or without concomitant MTX, and in patients with psoriasis, particularly when psoriatic arthropathy is a major cause for concern.[7,8] Secukinumab, a human monoclonal antibody that directly inhibits interleukin (IL)-17A, has demonstrated sustained clinical efficacy in the key clinical manifestations of PsA, in addition to improvement in physical function, HRQoL and inhibition of radiographic progression. In the treatment of patients with moderate-to-severe plaque psoriasis, secukinumab has shown greater efficacy vs. etanercept (TNF inhibitor) and ustekinumab (IL-12/23 inhibitor).[9–13]

Both adalimumab and secukinumab have been proven to be effective options for the treatment of patients with active PsA with or without the use of concomitant MTX.[8,10,14] However, approximately 40% of patients treated with MTX stop treatment owing to poor tolerability and/or toxicity problems, or cannot be treated with MTX, because of hepatic abnormalities related to PsA or concomitant alcohol abuse.[6,15,16]

EXCEED is the first double-blind head-to-head study to evaluate the efficacy and safety of secukinumab vs. adalimumab as a first-line biological monotherapy in patients with active PsA who were naïve to bDMARDs for PsA and psoriasis, and who were intolerant or had an inadequate response to csDMARDs. The results of the study showed that secukinumab narrowly missed statistical significance for superiority vs. adalimumab in the primary endpoint of American College of Rheumatology (ACR) 20 response at week 52; ACR 20 responses at week 52 were 67·4% with secukinumab vs. 61·5% with adalimumab (P = 0·071).[17] Secukinumab provided numerically higher (not statistically significant) clinical responses across musculoskeletal, skin and composite indices outcomes, with a higher retention rate than adalimumab at week 52.[17] Here, we report 52-week results from prespecified analyses in patients with PsA who had concomitant moderate-to-severe plaque psoriasis from the EXCEED study.