Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and clinical outcomes

Egwuagu, 2009, STAT3 in CD4+ T helper cell differentiation and inflammatory diseases, Cytokine, 47, 149, 10.1016/j.cyto.2009.07.003

Leonard, 1998, Jaks and STATs: biological implications, Annual Review of Immunology, 16, 293, 10.1146/annurev.immunol.16.1.293

O’Sullivan, 2007, Cytokine receptor signaling through the Jak–Stat–Socs pathway in disease, Molecular Immunology, 44, 2497, 10.1016/j.molimm.2006.11.025

Kawamura, 1994, Molecular cloning of L-JAK, a Janus family protein–tyrosine kinase expressed in natural killer cells and activated leukocytes, Proceedings of The National Academy of Sciences of the United States of America, 91, 6374, 10.1073/pnas.91.14.6374

Nosaka, 1995, Defective lymphoid development in mice lacking Jak3, Science, 270, 800, 10.1126/science.270.5237.800

Thomis, 1995, Defects in B lymphocyte maturation and T lymphocyte activation in mice lacking Jak3, Science, 270, 794, 10.1126/science.270.5237.794

Macchi, 1995, Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID), Nature, 377, 65, 10.1038/377065a0

Russell, 1995, Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development, Science, 270, 797, 10.1126/science.270.5237.797

Li X, Jesson M, Lee J et al. Characterization of a potent inhibitor of JAK kinases, CP-690,550, and inhibition of specific JAK/STAT pathways at efficacious exposures in a rodent model of arthritis. Abstract presented at the 15th International Inflammation Research Association Conference, Chantilly, Virginia, September 21-24, 2008.

Paniagua, 2005, Effects of JAK3 inhibition with CP-690,550 on immune cell populations and their functions in nonhuman primate recipients of kidney allografts, Transplantation, 80, 1283, 10.1097/01.tp.0000177643.05739.cd

Borie, 2005, Immunosuppression by the JAK3 inhibitor CP-690,550 delays rejection and significantly prolongs kidney allograft survival in nonhuman primates, Transplantation, 79, 791, 10.1097/01.TP.0000157117.30290.6F

Rousvoal, 2006, Janus kinase 3 inhibition with CP-690,550 prevents allograft vasculopathy, Transplant International, 19, 1014, 10.1111/j.1432-2277.2006.00387.x

Kudlacz, 2004, The novel JAK-3 inhibitor CP-690550 is a potent immunosuppressive agent in various murine models, American Journal of Transplantation, 4, 51, 10.1046/j.1600-6143.2003.00281.x

Rousvoal, 2004, JAK3 inhibition with CP-690,550 prevents obliterative bronchiolitis in a rat tracheal transplant model, Transplantation, 78, 46, 10.1097/00007890-200407271-00133

Kudlacz, 2008, The JAK-3 inhibitor CP-690550 is a potent anti-inflammatory agent in a murine model of pulmonary eosinophilia, European Journal of Pharmacology, 582, 154, 10.1016/j.ejphar.2007.12.024

Lawendy, 2009, Effect of CP-690,550, an orally active janus kinase inhibitor, on renal function in healthy adult volunteers, Journal of Clinical Pharmacology, 49, 423, 10.1177/0091270008330982

Krishnaswami, 2009, Effect of CYP2C19 polymorphism on the pharmacokinetics of CP-690,550, a Janus kinase inhibitor, The AAPS Journal, 11, 36

Hutmacher, 2008, Exposure-response modeling using latent variables for the efficacy of a JAK3 inhibitor administered to rheumatoid arthritis patients, Journal of Pharmacokinetics and Pharmacodynamics, 35, 139, 10.1007/s10928-007-9080-2

Prakash, 2008, Metabolism, pharmacokinetics and excretion of a Janus kinase-3 inhibitor, CP-690,550, in healthy male volunteers, The AAPS Journal, 10, 2492

Chow, 2008, Open label study to estimate the effect of fluconazole on the pharmacokinetics of a JAK3 antagonist (CP-690,550) in healthy adult subjects, Clinical Pharmacology And Therapeutics, 83

Chow, 2008, Open label study of the pharmacokinetics of a JAK3 antagonist (CP-690,550) and single doses of oral methotrexate in rheumatoid arthritis subjects, Clinical Pharmacology And Therapeutics, 83

Kremer, 2009, The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dose levels of CP-690,550 versus placebo, Arthritis and Rheumatism, 60, 1895, 10.1002/art.24567

Prevoo, 1995, Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis, Arthritis and Rheumatism, 38, 44, 10.1002/art.1780380107

van Gestel, 1996, Arthritis and Rheumatism, 39, 34, 10.1002/art.1780390105

Coombs, 2010, Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial, Annals of The Rheumatic Diseases, 69, 413, 10.1136/ard.2009.108159

Kremer, 2009, Safety and efficacy after 24 week (WK) dosing of the oral JAK inhibitor CP-690,550 (CP) in combination with methotrexate (MTX) in patients (PTS) with active rheumatoid arthritis (RA), Arthritis and Rheumatism, 60, 1925

Kremer JM, Cohen S, Wilkinson B et al. The oral Jak inhibitor CP-690,550 (CP) in combination with methotrexate (MTX) is efficacious, safe and well tolerated in patients with active rheumatoid arthritis (RA) with an inadequate response to methotrexate alone. Abstract presented at the American College of Rheumatology, San Francisco, California, October 24-29, 2008.

Wallenstein, 2009, Effects of the oral jak inhibitor CP-690,550 (CP) on pain, physical functioning (PF), fatigue, and health-related quality of life (HRQoL) in patients (pts) with active rheumatoid arthritis (RA), Arthritis and Rheumatism, 60, 418

Fleischmann, 2009, Safety and efficacy after 24 week (wk) dosing of the oral JAK inhibitor CP-690,550 (CP) as monotherapy in patients (pts) with active rheumatoid arthritis (RA), Arthritis and Rheumatism, 60, 1924

Kanik, 2009, Phase 2B dose ranging monotherapy study of the oral JAK inhibitor CP-690,550 (CP) or adalimumab (ADA) vs placebo (PBO) in patients (pts) with active rheumatoid arthritis (RA) with an inadequate response to DMARDs, Annals of The Rheumatic Diseases, 68, 123

Tanaka Y, Suzuki M, Nakamura H et al. The oral JAK inhibitor CP-690,550 (CP) in combination with methotrexate (MTX) is efficacious, safe and well tolerated in Japanese patients (pts) with active rheumatoid arthritis (RA) with an inadequate response to MTX alone. Abstract presented at the The European League Against Rheumatism, Copenhagen, Denmark, June 10-13, 2009.

Connell, 2009, Long-term follow-up of patients (pts) with moderate to severe rheumatoid arthritis (RA) treated with the oral JAK inhibitor CP-690,550 (CP), Annals of The Rheumatic Diseases, 68, 131

Boy, 2009, Double-blind, placebo-controlled, dose-escalation study to evaluate the pharmacologic effect of cp-690,550 in patients with psoriasis, The Journal of Investigative Dermatology, 129, 2299, 10.1038/jid.2009.25

Busque, 2009, Calcineurin-inhibitor-free immunosuppression based on the JAK inhibitor CP690,550: a pilot study in de novo kidney allograft recipients, American Journal of Transplantation, 9, 1936, 10.1111/j.1600-6143.2009.02720.x