Placebo-Controlled Trial of Tofacitinib Monotherapy in Rheumatoid Arthritis

• Published in: The New England journal of medicine Vol. 367; no. 6; pp. 495 - 507
• Main Authors: Fleischmann, Roy, Kremer, Joel, Cush, John, Schulze-Koops, Hendrik, Connell, Carol A, Bradley, John D, Gruben, David, Wallenstein, Gene V, Zwillich, Samuel H, Kanik, Keith S
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 09-08-2012
• Subjects: Activities of Daily Living; Adult; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Biological and medical sciences; Cholesterol; Disability Evaluation; Diseases of the osteoarticular system; Double-Blind Method; Drug dosages; Drug therapy; Enzyme inhibitors; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - therapeutic use; Erythrocyte sedimentation rate; Female; General aspects; Headache; Hepatitis; Humans; Infections; Inflammatory joint diseases; Janus kinase; Janus Kinase 3 - antagonists & inhibitors; Least-Squares Analysis; Leukocyte Count; Male; Medical sciences; Middle Aged; Neutrophils; Patients; Piperidines; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Pyrroles - adverse effects; Pyrroles - therapeutic use; Respiratory tract diseases; Rheumatic diseases; Rheumatoid arthritis; Severity of Illness Index; Treatment Outcome; Medicine; Immunopathology; Chronic; Rheumatoid arthritis; Diseases of the osteoarticular system; Placebo; Autoimmune disease; Clinical trial; Inflammatory joint disease; Monotherapy
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1109071

In a placebo-controlled trial, monotherapy with tofacitinib, an oral Janus kinase inhibitor, reduced the symptoms and signs of rheumatoid arthritis. Adverse events associated with tofacitinib included infections, decreased neutrophil counts, and elevated LDL cholesterol levels.
Rheumatoid arthritis is a chronic autoimmune disease that is characterized by inflammation and destruction of joints. The disease has a major effect on health status and quality of life and imposes a substantial economic burden on patients and society.
1
Tofacitinib (CP-690,550) is a novel oral Janus kinase (JAK) inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis. Tofacitinib preferentially inhibits signaling through heterodimeric receptors associated with JAK3, JAK1, or both, with functional selectivity over JAK2-paired receptors.
2
Inhibition of JAK1 and JAK3 by tofacitinib blocks signaling for several cytokines (interleukins 2, 4, 7, 9, 15, . . .