Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial

Arthritis Research and Therapy

Volumn 14, Issue 1, 2012, Pages

  Fleishaker, Dona L ^a   Garcia Meijide, Juan A ^b   Petrov, Andriy ^c   Kohen, Michael D ^d   Wang, Xin ^a   Menon, Sujatha ^a   Stock, Thomas C ^a   Mebus, Charles A ^a   Goodrich, James M ^e   Mayer, Howard B ^f   Zeiher, Bernhardt G ^g  

^a PFIZER INC   (United States)

^b Hospital Ntra Sra de la Esperanza   (Spain)

^c V I VERNADSKY CRIMEAN FEDERAL UNIVERSITY   (Russian Federation)

^d Avivoclin Clinical Services   (United States)

^e VIIV HEALTHCARE   (United States)

^f EMD SERONO INC   (United States)

^g Astellas US LLC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MARAVIROC; METHOTREXATE; ANTIRHEUMATIC AGENT; CHEMOKINE RECEPTOR CCR5; CYCLOHEXANE DERIVATIVE; TRIAZOLE DERIVATIVE;

ADULT; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; BACKACHE; CD4 LYMPHOCYTE COUNT; CD8+ T LYMPHOCYTE; CHILL; CLINICAL ARTICLE; CONSTIPATION; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; DYSPEPSIA; EARLY TERMINATION OF CLINICAL TRIAL; ELECTROCARDIOGRAM; FATIGUE; FEMALE; FEVER; HUMAN; HUMERUS FRACTURE; INFESTATION; LIVER FUNCTION; MALE; MAXIMUM PLASMA CONCENTRATION; MUSCLE SPASM; NAUSEA; OPEN STUDY; ORTHOSTATIC HYPOTENSION; PHASE 2 CLINICAL TRIAL; PHYSICAL EXAMINATION; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS; SIDE EFFECT; TIME TO MAXIMUM PLASMA CONCENTRATION; UPPER RESPIRATORY TRACT INFECTION; VITAL SIGN; AGED; CHEMICALLY INDUCED DISORDER; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; DOSE RESPONSE; DRUG ADMINISTRATION; DRUG ANTAGONISM; DRUG COMBINATION; METABOLIC CLEARANCE RATE; METABOLISM; MIDDLE AGED; TREATMENT FAILURE;

ADULT; AGED; AGED, 80 AND OVER; ANTIRHEUMATIC AGENTS; AREA UNDER CURVE; ARTHRITIS, RHEUMATOID; CONSTIPATION; CYCLOHEXANES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; MALE; METABOLIC CLEARANCE RATE; METHOTREXATE; MIDDLE AGED; NAUSEA; RECEPTORS, CCR5; TREATMENT FAILURE; TRIAZOLES; YOUNG ADULT;

EID: 84862776995     PISSN: 14786354     EISSN: 14786362     Source Type: Journal    
DOI: 10.1186/ar3685     Document Type: Article

References (31)

1. Gomez-Reino JJ, Pablos JL, Carreira PE, Santiago B, Serrano L, Vicario JL, Balsa A, Figueroa M, De Juan MD. Association of rheumatoid arthritis with a functional chemokine receptor, CCR5. Arthritis Rheum 1999, 42:989-992. 10.1002/1529-0131(199905)42:5<989::AID-ANR18>3.0.CO;2-U, 10323455.
2. Abel S, Back DJ, Vourvahis M. Maraviroc: pharmacokinetics and drug interactions. Antivir Ther 2009, 14:607-618.
3. Fadel H, Temesgen Z. Maraviroc. Drugs Today (Barc) 2007, 43:749-758.
4. Meanwell NA, Kadow JF. Maraviroc, a chemokine CCR5 receptor antagonist for the treatment of HIV infection and AIDS. Curr Opin Investig Drugs 2007, 8:669-681.
5. Lieberman-Blum SS, Fung HB, Bandres JC. Maraviroc: a CCR5-receptor antagonist for the treatment of HIV-1 infection. Clin Ther 2008, 30:1228-1250. 10.1016/S0149-2918(08)80048-3, 18691983.
6. Castellino F, Huang AY, tan-Bonnet G, Stoll S, Scheinecker C, Germain RN. Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction. Nature 2006, 440:890-895. 10.1038/nature04651, 16612374.
7. Luther SA, Cyster JG. Chemokines as regulators of T cell differentiation. Nat Immunol 2001, 2:102-107. 10.1038/84205, 11175801.
8. Haringman JJ, Smeets TJM, Reinders-Blankert P, Tak PP. Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis. Ann Rheum Dis 2006, 65:294-300. 10.1136/ard.2005.037176, 1798063, 16107514.
9. Mack M, Bruhl H, Gruber R, Jaeger C, Cihak J, Eiter V, Plachy J, Stangassinger M, Uhlig K, Schattenkirchner M, Schlondorff D. Predominance of mononuclear cells expressing the chemokine receptor CCR5 in synovial effusions of patients with different forms of arthritis. Arthritis Rheum 1999, 42:981-988. 10.1002/1529-0131(199905)42:5<981::AID-ANR17>3.0.CO;2-4, 10323454.
10. Patel DD, Zachariah JP, Whichard LP. CXCR3 and CCR5 ligands in rheumatoid arthritis synovium. Clin Immun 2000, 98:39-45.
11. Ruth JH, Rottman JB, Katschke KJ, Qin S, Wu L, LaRossa G, Ponath P, Pope RM, Koch AE. Selective lymphocyte chemokine receptor expression in the rheumatoid joint. Arthritis Rheum 2001, 44:2750-2760. 10.1002/1529-0131(200112)44:12<2750::AID-ART462>3.0.CO;2-C, 11762935.
12. Vierboom MPM, Zavodny PJ, Chou C, Tagat JR, Pugliese-Sivo C, Strizki J, Steensma RW, McCombie SW, elebi-Paul L, Remarque E, Jonker M, Narula SK, Hart B. Inhibition of the development of collagen-induced arthritis in rhesus monkeys by a small molecular weight antagonist of CCR5. Arthritis Rheum 2005, 52:627-636. 10.1002/art.20850, 15693002.
13. Shahrara S, Proudfoot AE, Woods JM, Ruth JH, Amin MA, Park CC, Haas CS, Pope RM, Haines GK, Zha YY, Koch AE. Amelioration of Rat Adjuvant-Induced Arthritis by Met RANTES. Arthritis Rheum 2005, 52:1907-1919. 10.1002/art.21033, 1282452, 15934086.
14. Pokorny V, McQueen F, Yeoman S, Merriman M, Merriman A, Harrison A, Highton J, McLean L. Evidence for negative association of the chemokine receptor CCR5 d32 polymorphism with rheumatoid arthritis. Ann Rheum Dis 2005, 64:487-490. 1755415, 15331395.
15. Prahalad S. Negative association between the chemokine receptor CCR5-Delta 32 polymorphism and rheumatoid arthritis: a meta-analysis. Genes Immun 2006, 7:264-268. 10.1038/sj.gene.6364298, 3104293, 16541097.
16. Rossol M, Pierer M, Arnold S, KeyBer G, Burkhardt H, Baerwald C, Wagner U. Negative association of the chemokine receptor CCR5 d32 polymorphism with systemic inflammatory response, extra-articular symptoms and joint erosion in rheumatoid arthritis. Arthritis Res Ther 2009, 11:R91. 10.1186/ar2733, 2714147, 19538721.
17. Kohem CL, Brenol JC, Xavier RM, Bredemeier M, Brenol CV, Dedavid e Silva TL, de Castilhos Mello A, Canedo AD, Neves AG, Chies JAB. The chemokine receptor CCR5 genetic polymorphism and expression in rheumatoid arthritis patients. Scand J Rheumatol 2007, 36:359-364. 10.1080/03009740701393999, 17963165.
18. Zapico I, Coto E, Rodriguez A, Torre JC, Alvarez V. CCR5 (chemokine receptor-5) DNA-polymorphism influences the severity of rheumatoid arthritis. Genes Immun 2000, 1:288-289. 10.1038/sj.gene.6363673, 11196706.
19. Lan KK, Lachin JM, Bautista O. Over-ruling a group sequential boundary--a stopping rule versus a guideline. Stat Med 2003, 22:3347-3355. 10.1002/sim.1636, 14566919.
20. van Kuijk AW, Vergunst CE, Gerlag DM, Bresnihan B, Gomez-Reino JJ, Rouzier R, Verschueren PC, van de Leij C, Maas M, Kraan MC, Tak PP. CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo-controlled clinical trial. Ann Rheum Dis 2010, 69:2013-2016. 10.1136/ard.2010.131235, 20693270.
21. Rosario MC, Jacqmin P, Dorr P, James I, Jenkins TM, Abel S, Van Der Ryst E. Population pharmacokinetic/pharmacodynamic analysis of CCR5 receptor occupancy by maraviroc in healthy subjects and HIV-positive patients. Br J Clin Pharmacol 2008, 65(Suppl 1):86-94. 2311409, 18333870.
22. Leech M, Hutchinson P, Holdsworth SR, Morand EF. Endogenous glucocorticoids modulate neutrophil migration and synovial P-selectin but not neutrophil phagocytic or oxidative function in experimental arthritis. Clin Exp Immunol 1998, 112:383-388. 10.1046/j.1365-2249.1998.00601.x, 1905001, 9649205.
23. Goulding NJ, Euzger HS, Butt SK, Perretti M. Novel pathways for glucocorticoid effects on neutrophils in chronic inflammation. Inflamm Res 1998, 47(Suppl 3):S158-S165.
24. US Food and Drug Adminstration SELZENTRY (maraviroc) tablets Highlights of Prescribing Information. 2009, US Food and Drug Adminstration., http://www accessdata fda gov/drugsatfda_docs/label/2007/022128lbl pdf
25. Abel S, van der Ryst E, Rosario MC, Ridgway CE, Medhurst CG, Taylor-Worth RJ, Muirhead GJ. Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel CCR5 antagonist, in healthy volunteers. Br J Clin Pharmacol 2008, 65(Suppl 1):5-18. 2311414, 18333861.
26. Yost R, Pasquale TR, Sahloff EG. Maraviroc: a coreceptor CCR5 antagonist for management of HIV infection. Am J Health Syst Pharm 2009, 66:715-726. 10.2146/ajhp080206, 19336831.
27. Gulick RM, Lalezari J, Goodrich J, Clumeck N, DeJesus E, Horban A, Nadler J, Clotet B, Karlsson A, Wohlfeiler M, Montana JB, McHale M, Sullivan J, Ridgway C, Felstead S, Dunne MW, van der Ryst E, Mayer H, . the MOTIVATE Study Teams Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med 2008, 359:1429-1441. 10.1056/NEJMoa0803152, 3078519, 18832244, the MOTIVATE Study Teams.
28. Emmelkamp JM, Rockstroh JK. CCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature. Eur J Med Res 2007, 12:409-417.
29. Ryan CT. Trials of aplaviroc halted in treatment-naive patients. AIDS Clin Care 2005, 17:107-108.
30. Nichols WG, Steel HM, Bonny T, Adkison K, Curtis L, Millard J, Kabeya K, Clumeck N. Hepatotoxicity observed in clinical trials of aplaviroc (GW873140). Antimicrob Agents Chemother 2008, 52:858-865. 10.1128/AAC.00821-07, 2258506, 18070967.
31. Ndegwa S. Maraviroc (Celsentri) for multidrug-resistant human immunodeficiency virus (HIV)-1. Issues Emerg Health Technol 2007, (110):1-8.