A 24-week, randomized, double-blind, placebo-controlled, parallel group study of the efficacy of oral SCIO-469, a p38 mitogen-activated protein kinase inhibitor, in patients with active rheumatoid arthritis

Journal of Rheumatology

Volumn 38, Issue 5, 2011, Pages 846-854

  Genovese, Mark C ^a   Cohen, Stanley B ^b   Wofsy, David ^c   Weinblatt, Michael E ^d   Firestein, Gary S ^c   Brahn, Ernest ^c   Strand, Vibeke ^a   Baker, Daniel G ^e   Tong, Sandra E ^f,g  

^a STANFORD UNIVERSITY   (United States)

^b METROPLEX CLINICAL RESEARCH CENTER   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d BRIGHAM AND WOMEN S HOSPITAL   (United States)

^e CENTOCOR INC   (United States)

^f SCIOS INC   (United States)

^g AFFYMAX RESEARCH INSTITUTE   (United States)

Author keywords

Clinical trials; P38 mitogen activated protein kinase; Rheumatoid arthritis

Indexed keywords

ACUTE PHASE PROTEIN; C REACTIVE PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE P38; PLACEBO; TALMAPIMOD;

ACNE; ACUTE GRANULOCYTIC LEUKEMIA; ADULT; ARTHRALGIA; ARTICLE; ASTHMA; BRONCHITIS; CELLULITIS; CLOSTRIDIUM INFECTION; COLITIS; CONGESTIVE HEART FAILURE; CONTROLLED RELEASE FORMULATION; CONTROLLED STUDY; COUGHING; DEEP VEIN THROMBOSIS; DIARRHEA; DIVERTICULITIS; DIZZINESS; DOSAGE SCHEDULE COMPARISON; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG ERUPTION; DRUG SAFETY; DRUG TOLERABILITY; DUODENUM ULCER; ERYTHROCYTE SEDIMENTATION RATE; FEMALE; GENERALIZED EDEMA; HEART ATRIUM FIBRILLATION; HEART INFARCTION; HUMAN; HYPERGLYCEMIA; INFECTION; ISCHEMIC COLITIS; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; PNEUMONIA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY FAILURE; RHEUMATOID ARTHRITIS; SIDE EFFECT; SINUSITIS; SYNCOPE; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; VIRAL GASTROENTERITIS;

ADMINISTRATION, ORAL; ADULT; AGED; ARTHRITIS, RHEUMATOID; BLOOD SEDIMENTATION; C-REACTIVE PROTEIN; DOUBLE-BLIND METHOD; FEMALE; HUMANS; INDOLES; MALE; MIDDLE AGED; P38 MITOGEN-ACTIVATED PROTEIN KINASES; SEVERITY OF ILLNESS INDEX; TREATMENT OUTCOME;

EID: 79955563297     PISSN: 0315162X     EISSN: 14992752     Source Type: Journal    
DOI: 10.3899/jrheum.100602     Document Type: Article

References (23)

1. Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 1996;14:397-440. (Pubitemid 26130190)
2. Enbrel: Package insert. Thousand Oaks, CA: Immunex; 2006.
3. Humira: Package insert. Abbott Park, IL: Abbott Laboratories; 2006.
4. Remicade: Package insert. Malvern, PA: Centocor Inc.; 2007.
5. Beyaert R, Cuenda A, Vanden Berghe W, Plaisance S, Lee JC, Haegeman G, et al. The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor. EMBO J 1996;15:1914-23. (Pubitemid 26119694)
6. Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D, et al. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 1994;372:739-46.
7. Schett G, Tohidast-Akrad M, Smolen JS, Schmid BJ, Steiner CW, Bitzan P, et al. Activation, differential localization, and regulation of the stress-activated protein kinases, extracellular signal-regulated kinase, c-JUN N-terminal kinase, and p38 mitogen-activated protein kinase, in synovial tissue and cells in rheumatoid arthritis. Arthritis Rheum 2000;43:2501-12.
8. Thalhamer T, McGrath MA, Harnett MM. MAPKs and their relevance to arthritis and inflammation. Rheumatology 2008;47:409-14.
9. Nishikawa M, Myoui A, Tomita T, Takahi K, Nampei A, Yoshikawa H. Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis Rheum 2003;48:2670-81. (Pubitemid 37129445)
10. Amakye D, Tong S, Ward C, Beazley W. Pharmacokinetics (PK) and pharmacodynamics (PD) of SCIO-469, a p38a MAP kinase inhibitor. Clin Pharmacol Ther 2004;75:P54.
11. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.
12. Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolfe F. The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum 1992;35:498-502.
13. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38:727-35.
14. Cohen SB, Cheng TT, Chindalore V, Damjanov N, Burgos-Vargas R, Delora P, et al. Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis. Arthritis Rheum 2009;60:335-44.
15. Damjanov N, Kauffman RS, Spencer-Green GT. Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum 2009;60:1232-41.
16. Genovese MC. Inhibition of p38: has the fat lady sung? Arthritis Rheum 2009;60:317-20.
17. Kelly J. Array BioPharma stops work on ARRY-797 pan-cytokine inhibitor for RA despite good early data. Musculoskeletal Report [Internet. July 16, 2009. Accessed Dec 10, 2010] Available from: http://www.mskreport.com/articles.cfm? articleID=3390
18. Hammaker D, Sweeney S, Firestein GS. Signal transduction networks in rheumatoid arthritis. Ann Rheum Dis 2003;62 Suppl 2:ii86-9.
19. Schreiber S, Feagan B, D'Haens G, Colombel JF, Geboes K, Yurcov M, et al. Oral p38 mitogen-activated protein kinase inhibition with BIRB 796 for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 2006;4:325-34. (Pubitemid 43343889)
20. Kim C, Sano Y, Todorova K, Carlson BA, Arpa L, Celada A, et al. The kinase p38 alpha serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression. Nat Immunol 2008;9:1019-27.
21. Boyle DL, Jones TL, Hammaker D, Svensson CI, Rosengren S, Albani S, et al. Regulation of peripheral inflammation by spinal p38 MAP kinase in rats. PLoS Med 2006;3:e338.
22. Weinblatt ME, Kavanaugh A, Burgos-Vargas R, Dikranian AH, Medrano-Ramirez G, Morales-Torres JL, et al. Treatment of rheumatoid arthritis with a Syk kinase inhibitor: a twelve-week, randomized, placebo-controlled trial. Arthritis Rheum 2008;58:3309-18.
23. Kremer JM, Bloom BJ, Breedveld FC, Coombs JH, Fletcher MP, Gruben D, et al. 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 dosage levels of CP-690,550 versus placebo. Arthritis Rheum 2009;60:1895-905.