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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterised by infiltration of immune cells into the affected synovium, release of inflammatory cytokines and degradative mediators, and subsequent joint damage. Both innate and adaptive arms of the immune response play a role, with activation of immune cells leading to dysregulated expression of inflammatory cytokines. Cytokines work within a complex regulatory network in RA, signalling through different intracellular kinase pathways to modulate recruitment, activation and function of immune cells and other leukocytes. As our understanding of RA has advanced, intracellular signalling pathways such as Janus kinase (JAK) pathways have emerged as key hubs in the cytokine network and, therefore, important as therapeutic targets. Tofacitinib is an oral JAK inhibitor for the treatment of RA. Tofacitinib is a targeted small molecule, and an innovative advance in RA therapy, which modulates cytokines critical to the progression of immune and inflammatory responses. Herein we describe the mechanism of action of tofacitinib and the impact of JAK inhibition on the immune and inflammatory responses in RA.

To evaluate the efficacy and safety of celecoxib in patients with ankylosing spondylitis (AS).This was a 12-week randomized, double-blind, placebo-controlled study with 4 treatment arms: celecoxib 200 mg qd, celecoxib 400 mg qd, naproxen 500 mg bid, and placebo. Patients (age 18-75 yrs) requiring daily treatment with nonselective nonsteroidal antiinflammatory drugs, and with a pain intensity on visual analog scale (VAS)or = 50 mm worsening by 30% compared with a preinclusion visit (14 days prior) were studied. Primary endpoints were least-squares mean changes from baseline in pain intensity, disease activity (patient global assessment VAS), and functional impairment [Bath Ankylosing Spondylitis Functional Index (BASFI)]. Adverse events were monitored throughout the study.Of 611 randomized patients, 137 were allocated to celecoxib 200 mg, 161 to celecoxib 400 mg, 157 to naproxen, and 156 to placebo. Improvements in least-squares mean pain intensity, disease activity, and BASFI scores were significantly greater in the celecoxib 200 mg, celecoxib 400 mg, and naproxen groups than in the placebo group (por = 0.001) at Week 12 and the interim timepoints, Weeks 1, 3, and 6. Celecoxib 400 mg was as effective as naproxen; however, naproxen was more effective than celecoxib 200 mg. Celecoxib was well tolerated, with an adverse event profile similar to placebo. However, 3 naproxen-treated patients experienced serious treatment-related gastrointestinal (GI) adverse events (one severe gastric ulcer, one moderate GI hemorrhage, one severe GI hemorrhage).In this 12-week study, celecoxib 200 mg qd and 400 mg qd were efficacious and well tolerated in treating signs and symptoms of AS.