Efficacy and Safety of Ivarmacitinib Monotherapy in the Treatment of csDMARDs-IR Rheumatoid Arthritis

Prior treatment

• Requiring continued combination therapy with methotrexate (MTX), hydroxychloroquine, and sulfasalazine, or any combination of three csDMARDs;
• Subjects who have previously received a standard course of JAK inhibitors (e.g., tofacitinib, upadacitinib, baricitinib, filgotinib, deucravacitinib, etc., including topical formulations) and have primary failure to biologic DMARDs (bDMARDs) treatment;
• Subjects with moderate to severe congestive heart failure (New York Heart Association Class III or IV), or those who have experienced a cardiovascular or cerebrovascular event requiring hospitalization within 6 months prior to enrollment, including but not limited to percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, cerebral hemorrhage, or subarachnoid hemorrhage;
• Subjects who have received a live/attenuated vaccine within the previous 3 months or are expected to receive a live/attenuated vaccine during the study period or within 28 days after the end of the study;
• Subjects who have participated in another clinical trial within 30 days prior to the screening period;

Other illness

• Subjects judged by the investigator to have active symptoms of primary fibromyalgia or other conditions that may interfere with the assessment of RA symptoms;
• Subjects with a current or history of malignancy (except for adequately treated or excised non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin, or cervical carcinoma in situ);
• Subjects considered by the investigator to have any other conditions that make them unsuitable for participation in this study.

Lab values

• Subjects with uncontrolled infections, such as hepatitis B carriers with liver dysfunction (aspartate aminotransferase or alanine aminotransferase ≥ 3 times the upper limit of the laboratory normal range, or bilirubin ≥ 1.5 times the upper limit of the laboratory normal range); subjects with a history of latent or active tuberculosis who have not completed an adequate course of anti-tuberculosis treatment; subjects with symptomatic herpes zoster infection;
• Subjects with an estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m² calculated by the Modified Diet in Renal Disease (MDRD) formula or other methods;

Other

• Lactating or pregnant women, or fertile subjects unwilling to take effective contraceptive measures throughout the trial period and for 1 month after the last administration of emmacitinib tablets;
• Subjects who refuse to sign the informed consent form or are unwilling or unable to cooperate with the collection of medical history and clinical photographs;

• Aged between 18 and 75 years (inclusive) at the time of signing the informed consent form, regardless of gender;
• Meeting the diagnostic criteria for rheumatoid arthritis (RA) as defined in the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for RA;
• Having moderate to severe active RA, defined as having a tender joint count (TJC) ≥ 6 or a swollen joint count (SJC) ≥ 6 based on a 68/66-joint count at screening, or a Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28 ESR)/C-reactive protein (CRP) ≥ 3.2, and having an ESR \> 28 mm/h or CRP/high-sensitivity CRP (hsCRP) \> 5 mg/L at screening;
• Having an inadequate response to or intolerance of at least one or more conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Subjects must have received regular csDMARD therapy for at least 3 months and have been on a stable dose for at least 4 weeks prior to initiating study drug treatment. Allowable csDMARDs include methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide, among others.