Among patients with psoriatic arthritis (PsA), secukinumab provides early and sustained resolution of enthesitis, according to study results published in Arthritis Research and Therapy. Compared with secukinumab 150 mg, secukinumab 300 mg showed higher resolution in patients with a more severe baseline enthesitis count.
Patients with PsA and enthesitis experience worse outcomes than patients without enthesitis. This post hoc analysis of pooled data from the FUTURE 2 and 3 studies (ClinicalTrials.gov Identifiers: NCT01752634 and NCT01989468, respectively) explored the effect of secukinumab on enthesitis resolution in patients with PsA.
Data analyzed included a full resolution of enthesitis count (EC=0) and median time to first resolution of enthesitis, using the Kaplan-Meier estimate. Efficacy outcomes included response rates measured by the American College of Rheumatology (ACR) and Psoriasis Area and Severity Index (PASI) response rates and by mean changes from baseline in Short Form 36 Physical Component Summary score (SF-36 PCS), Health Assessment Questionnaire Disability Index (HAQ-DI), and 28-Joint Disease Activity Score using C-reactive protein (DAS28-CRP). These outcomes were assessed in patients both with and without baseline enthesitis.
Of the 712 patients included in pooled analysis, 466 (65%) were diagnosed with enthesitis at baseline (secukinumab 150 mg, 159/238; secukinumab 300 mg, 144/239; and placebo, 163/235), and approximately two-thirds were naive to tumor necrosis factor inhibitor (TNFi) therapy. Kaplan-Meier analysis indicated that 65% of patients who received secukinumab 300 mg achieved full resolution of EC at week 16, along with 56% of those who received 150 mg, and 44% of those who received placebo. At week 104, response rates for full resolution improved to 88% and 91% with secukinumab 150 mg and 300 mg, respectively. Median time to full resolution was shorter with secukinumab compared with placebo in the overall population (57 and 85 days vs 167 days, respectively), in TNFi-naive patients (57 and 85 days vs 120 days, respectively), and TNFi-inadequate response patients (92 and 82 days vs 169 days, respectively). The majority of patients without baseline enthesitis did not develop enthesitis at week 16 (86% with secukinumab 300 mg, 95% with 150 mg, and 83% with placebo), which was maintained at week 104 (89% with both 300 mg and 150 mg).
At week 16, patients with baseline enthesitis who received secukinumab 300 mg and 150 mg showed better outcomes than those who received placebo for ACR20 (51.6% and 44.3% vs 19.5%, respectively), ACR50 (31.4% and 21.0% vs 7.5%, respectively), PASI 90 (66.5% and 51.8% vs 13.1%, respectively), HAQ-DI (-0.5 and -0.3 vs -0.2, respectively), DAS28-CRP (-1.4 and -1.0 vs -0.5), and SF-36 PCS (6.1 and 3.5 vs 2.3, respectively). Among patients without baseline enthesitis, secukinumab 300 mg and 150 mg also showed higher responses compared with placebo for ACR20 (48.8% and 60.4% vs 13.8%), ACR50 (32.6% and 32.9% vs 4.1%), and PASI 90 (56.4% and 48.9% vs 10.8%), with improved physical function and health-related quality of life (HAQ-DI, -0.4 and -0.5 vs -0.2; SF-36 PCS, 6.1 and 7.0 vs 2.0), and reduced disease activity (DAS28-CRP, -1.3 and -1.5 vs -0.4). Improvements for most outcome measures were sustained or further improved over 104 weeks with secukinumab in patients with and without enthesitis.
“This post hoc analysis further extends the evidence for an early and sustained efficacy of secukinumab on enthesitis in patients with PsA irrespective of previous TNFi exposure. Secukinumab 300 mg was associated with greater efficacy on enthesitis than 150 mg notably in patients with higher baseline EC. Although patients with enthesitis at baseline had higher disease activity, secukinumab improved outcomes across multiple clinical domains of PsA as early as week 16 and maintained efficacy over 2 years, with responses being similar to patients without enthesitis, especially with the secukinumab 300 mg dose,” the researchers concluded.
Disclosure: This clinical trial was supported by Novartis Pharma AG, Basel, Switzerland. Please see the original reference for a full list of authors’ disclosures.
Coates LC, Wallman JK, McGonagle D, et al. Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies. Arthritis Res Ther. 2019;21(1):266.