Clinical Research Directory

Ivarmacitinib With or Without Celecoxib for Ankylosing Spondylitis

Sponsor: Peking University Third Hospital

Summary

Background: Ankylosing spondylitis (AS) is a chronic, progressive inflammatory disease mainly affecting the spine and sacroiliac joints, causing pain, stiffness, structural damage, and functional disability. NSAIDs remain first-line therapy, while biologics and JAK inhibitors have expanded treatment options. However, many patients have inadequate responses or residual symptoms, and long-term combination with NSAIDs is common despite uncertain incremental benefit. Ivarmacitinib is a highly selective oral JAK1 inhibitor that has shown efficacy in active AS. Whether concomitant celecoxib adds benefit to ivarmacitinib monotherapy remains unknown. Objectives: To compare the efficacy and safety of ivarmacitinib plus celecoxib versus ivarmacitinib monotherapy in patients with active AS. The primary objective is to compare the proportion achieving an ASAS20 response at week 24. Methods: This prospective, single-center, randomized, open-label, parallel-group, active-controlled superiority trial will enroll 138 patients with active AS (BASDAI ≥4 and total back pain VAS ≥4) who had inadequate response to at least two NSAIDs or intolerance/contraindication to NSAIDs. Participants will be randomized 1:1 to ivarmacitinib 4 mg once daily plus celecoxib 200 mg twice daily or ivarmacitinib 4 mg once daily for 48 weeks, with as-needed rescue analgesia permitted. The study is open-label, but endpoint assessors and the statistician will be blinded. Key exclusion criteria include prior JAK inhibitor use, major cardiovascular events, active peptic ulcer or bleeding, moderate-to-severe renal insufficiency, pregnancy, significant laboratory abnormalities, and malignancy within 5 years. Outcomes: The primary endpoint is the proportion achieving ASAS20 at week 24. Secondary endpoints include ASAS20 at weeks 12 and 48; ASAS40 and ASAS5/6; changes in BASDAI, ASDAS-CRP, CRP, ESR, BASMI, BASFI, pain VAS, ASQoL, MASES, GUESS, and SPARCC MRI score; rescue analgesic use; and adverse event incidence, type, severity, and relatedness, with attention to gastrointestinal, cardiovascular, renal, and infectious risks. Sample Size: Assuming a week-24 ASAS20 rate of 66.7% in the combination group, a 25-percentage-point superiority margin, two-sided α = 0.05, 80% power, and 15% dropout, 69 patients per group are required (total 138). Statistical Analysis: The full analysis set includes all randomized patients receiving at least one dose, analyzed as randomized. The primary analysis will compare week-24 ASAS20 proportions using a normal-approximation Z-test with 95% CI and p-value; significance is p ≤ 0.025 one-sided. Secondary categorical endpoints will use the Z-test with non-responder imputation; continuous variables will use MMRM or ANCOVA. Safety will be analyzed descriptively in the safety set. Expected Significance: This trial will provide prospective, head-to-head evidence on whether regular celecoxib adds benefit to ivarmacitinib monotherapy, informing individualized NSAID-JAK inhibitor combination decisions and supporting evidence-based optimization of AS treatment.

Official title: A Randomized Controlled Study Evaluating the Efficacy and Safety of Ivarmacitinib Combined With Celecoxib Versus Ivarmacitinib Monotherapy in Patients With Ankylosing Spondylitis

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