Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: Results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques

Annals of the Rheumatic Diseases

Volumn 75, Issue 6, 2016, Pages 1024-1033

  Conaghan, Philip G ^a   Østergaard, Mikkel ^b,c   Bowes, Michael A ^d   Wu, Chunying ^e   Fuerst, Thomas ^e   Van Der Heijde, Désirée ^f   Irazoque Palazuelos, Fedra ^g   Soto Raices, Oscar ^h   Hrycaj, Pawel ⁱ   Xie, Zhiyong ^j   Zhang, Richard ^j   Wyman, Bradley T ^j   Bradley, John D ^j   Soma, Koshika ^j   Wilkinson, Bethanie ^j  

^a UNIVERSITY OF LEEDS   (United Kingdom)

^b University of Copenhagen   (Denmark)

^c UNIVERSITY OF COPENHAGEN   (Denmark)

^d IMORPHICS LTD   (United Kingdom)

^e BioClinica Inc   (United States)

^f LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^g Centro de Investigación y Tratamiento Reumatológico S C   (Mexico)

^h Mindful Rheumatix   (Puerto Rico)

ⁱ POZNAN UNIVERSITY OF MEDICAL SCIENCES   (Poland)

^j PFIZER INC   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ASPARTATE AMINOTRANSFERASE; CREATINE KINASE; GAMMA GLUTAMYLTRANSFERASE; METHOTREXATE; PLACEBO; TOFACITINIB; ANTIRHEUMATIC AGENT; PIPERIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE;

ADULT; ALOPECIA; ARTICLE; BACKACHE; BONE EROSION; BONE MARROW EDEMA; BRONCHITIS; CONNECTIVE TISSUE DISEASE; CONTRAST ENHANCEMENT; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; DAS28; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG DOSE TITRATION; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; EXPLORATORY RESEARCH; FEMALE; GASTRITIS; GASTROENTERITIS; GASTROINTESTINAL DISEASE; HEADACHE; HEALTH ASSESSMENT QUESTIONNAIRE; HUMAN; HYPERTENSION; HYPERTRANSAMINASEMIA; HYPERTRIGLYCERIDEMIA; INFECTION; INFESTATION; INFLUENZA; MAJOR CLINICAL STUDY; MALE; MENORRHAGIA; MONOTHERAPY; MULTICENTER STUDY; MUSCULOSKELETAL DISEASE; NUCLEAR MAGNETIC RESONANCE IMAGING; PARALLEL DESIGN; PERIANAL ABSCESS; PHARYNGITIS; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; QUANTITATIVE RHEUMATOID ARTHRITIS MAGNETIC RESONANCE IMAGING SCORE; QUANTITATIVE STUDY; RANDOMIZED CONTROLLED TRIAL; RASH; RHEUMATOID ARTHRITIS; RHEUMATOID ARTHRITIS MAGNETIC RESONANCE IMAGING SCORE; RHINITIS; SCORING SYSTEM; SIDE EFFECT; SKIN DISEASE; SYNOVITIS; UPPER ABDOMINAL PAIN; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; VAN DER HEIJDE MODIFICATION OF THE TOTAL SHARP SCORE; WEIGHT GAIN; XEROSTOMIA; ARTHRITIS, RHEUMATOID; BONE DENSITY; BONE MARROW; BONE MARROW DISEASES; CLINICAL TRIAL; COMBINATION DRUG THERAPY; COMPLICATION; DIAGNOSTIC IMAGING; DISEASE COURSE; DRUG EFFECTS; EDEMA; HAND; MIDDLE AGED; TREATMENT OUTCOME; WRIST;

ADULT; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; BONE DENSITY; BONE MARROW; BONE MARROW DISEASES; DISEASE PROGRESSION; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; EDEMA; FEMALE; HAND; HUMANS; MAGNETIC RESONANCE IMAGING; MALE; METHOTREXATE; MIDDLE AGED; PIPERIDINES; PYRIMIDINES; PYRROLES; SYNOVITIS; TREATMENT OUTCOME; WRIST JOINT;

EID: 84962179941     PISSN: 00034967     EISSN: 14682060     Source Type: Journal    
DOI: 10.1136/annrheumdis-2015-208267     Document Type: Article

References (40)

1. Baker JF, Ostergaard M, Emery P, et al. Early MRI measures independently predict 1-year and 2-year radiographic progression in rheumatoid arthritis: secondary analysis from a large clinical trial. Ann Rheum Dis 2014;73:1968-74.
2. Hetland ML, Ejbjerg B, Hørslev-Petersen K, et al. MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2-year randomised controlled trial (CIMESTRA). Ann Rheum Dis 2009;68:384-90.
3. Haavardsholm EA, Bøyesen P, Østergaard M, et al. Magnetic resonance imaging findings in 84 patients with early rheumatoid arthritis: bone marrow oedema predicts erosive progression. Ann Rheum Dis 2008;67:794-800.
4. Bombardier C, Barbieri M, Parthan A, et al. The relationship between joint damage and functional disability in rheumatoid arthritis: a systematic review. Ann Rheum Dis 2012;71:836-44.
5. Strand V, Singh JA. Improved health-related quality of life with effective disease-modifying antirheumatic drugs: evidence from randomized controlled trials. Am J Manag Care 2007;13(Suppl 9):S237-51.
6. Fleischmann R, Cutolo M, Genovese MC, et al. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690, 550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum 2012;64:617-29.
7. Kremer JM, Bloom BJ, Breedveld FC, 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.
8. Kremer JM, Cohen S, Wilkinson BE, et al. A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690, 550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Arthritis Rheum 2012;64: 970-81.
9. Tanaka Y, Suzuki M, Nakamura H, et al. Phase II study of tofacitinib (CP-690, 550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Care Res (Hoboken) 2011;63:1150-8.
10. Tanaka Y, Takeuchi T, Yamanaka H, et al. Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, Phase 2 study. Mod Rheumatol 2015;25:514-21.
11. Burmester GR, Blanco R, Charles-Schoeman C, et al. Tofacitinib (CP-690, 550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet 2013;381:451-60.
12. Fleischmann R, Kremer J, Cush J, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med 2012;367:495-507.
13. Kremer J, Li ZG, Hall S, et al. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med 2013;159:253-61.
14. Lee EB, Fleischmann R, Hall S, et al. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med 2014;370:2377-86.
15. van der Heijde D, Tanaka Y, Fleischmann R, et al. Tofacitinib (CP-690, 550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis Rheum 2013;65:559-70.
16. van Vollenhoven RF, Fleischmann R, Cohen S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med 2012;367:508-19.
17. Wollenhaupt J, Silverfield J, Lee EB, et al. Tofacitinib, an Oral Janus Kinase Inhibitor, in the Treatment of Rheumatoid Arthritis: Safety and Clinical and Radiographic Efficacy in Open-Label, Long-Term Extension Studies over 7 Years [abstract]. Arthritis Rheum 2015;67(Suppl 10).
18. Peterfy C, Østergaard M, Conaghan PG. MRI comes of age in RA clinical trials. Ann Rheum Dis 2013;72:794-6.
19. Ejbjerg BJ, Vestergaard A, Jacobsen S, et al. The smallest detectable difference and sensitivity to change of magnetic resonance imaging and radiographic scoring of structural joint damage in rheumatoid arthritis finger, wrist, and toe joints: a comparison of the OMERACT rheumatoid arthritis magnetic resonance imaging score applied to different joint combinations and the Sharp/van der Heijde radiographic score. Arthritis Rheum 2005;52:2300-6.
20. American College of Rheumatology Rheumatoid Arthritis Clinical Trials Task Force Imaging GroupOutcome Measures in Rheumatology Magnetic Resonance Imaging Inflammatory Arthritis Working Group. Review: the utility of magnetic resonance imaging for assessing structural damage in randomized controlled trials in rheumatoid arthritis. Arthritis Rheum 2013;65:2513-23.
21. Axelsen MB, Eshed I, Hørslev-Petersen K, et al. A treat-to-target strategy with methotrexate and intra-articular triamcinolone with or without adalimumab effectively reduces MRI synovitis, osteitis and tenosynovitis and halts structural damage progression in early rheumatoid arthritis: results from the OPERA randomised controlled trial. Ann Rheum Dis2015;74:867-75.
22. Conaghan PG, Peterfy C, Olech E, et al. The effects of tocilizumab on osteitis, synovitis and erosion progression in rheumatoid arthritis: results from the ACT-RAY MRI substudy. Ann Rheum Dis 2014;73:810-16.
23. Durez P, Malghem J, Nzeusseu Toukap A, et al. Treatment of early rheumatoid arthritis: a randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone. Arthritis Rheum 2007;56:3919-27.
24. Haavardsholm EA, Østergaard M, Hammer HB, et al. Monitoring anti-TNFalpha treatment in rheumatoid arthritis: responsiveness of magnetic resonance imaging and ultrasonography of the dominant wrist joint compared with conventional measures of disease activity and structural damage. Ann Rheum Dis 2009;68:1572-9.
25. Kosta PE, Voulgari PV, Zikou AK, et al. Effect of very early treatment in rheumatoid arthritis on bone oedema and synovitis, using magnetic resonance imaging. Scand J Rheumatol 2012;41:339-44.
26. Peterfy C, Durez P, Haraoui B, et al. Response of early rheumatoid arthritis (RA) to treatment with adalimumab plus methotrexate vs. methotrexate alone: magnetic resonance imaging results from OPTIMA [abstract]. Ann Rheum Dis 2010;69(Suppl 3):455.
27. Conaghan PG, O'Connor P, McGonagle D, et al. Elucidation of the relationship between synovitis and bone damage: a randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis. Arthritis Rheum 2003;48:64-71.
28. Quinn MA, Conaghan PG, O'Connor PJ, et al. Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage, with sustained benefit after infliximab withdrawal: results from a twelve-month randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2005;52:27-35.
29. Døhn UM, Ejbjerg BJ, Hasselquist M, et al. Rheumatoid arthritis bone erosion volumes on CT and MRI: reliability and correlations with erosion scores on CT, MRI and radiography. Ann Rheum Dis 2007;66:1388-92.
30. Axelsen MB, Stoltenberg M, Poggenborg RP, et al. Dynamic gadolinium-enhanced magnetic resonance imaging allows accurate assessment of the synovial inflammatory activity in rheumatoid arthritis knee joints: a comparison with synovial histology. Scand J Rheumatol 2012;41:89-94.
31. Axelsen MB, Ejbjerg BJ, Hetland ML, et al. Differentiation between early rheumatoid arthritis patients and healthy persons by conventional and dynamic contrast-enhanced magnetic resonance imaging. Scand J Rheumatol 2014;43:109-18.
32. Axelsen MB, Poggenborg RP, Stoltenberg M, et al. Reliability and responsiveness of dynamic contrast-enhanced magnetic resonance imaging in rheumatoid arthritis. Scand J Rheumatol 2013;42:115-22.
33. Cootes TF, Edwards GJ, Taylor CJ. Active appearance models. IEEE Trans Pattern Anal Mach Intell 2001;23:681-5.
34. Bowes MA, Guillard G, Gill E, et al. Novel quantification of MRI provides a more sensitive outcome measure than Ramris [abstract]. Arthritis Rheumatol 2014;66: S517.
35. Østergaard M, Peterfy C, Conaghan P, et al. OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. J Rheumatol 2003;30:1385-6.
36. Bowes MA, Vincent GR, Wolstenholme CB, et al. A novel method for bone area measurement provides new insights into osteoarthritis and its progression. Ann Rheum Dis 2015;74:519-25.
37. Kubassova O, Boesen M, Boyle RD, et al. Fast and robust analysis of dynamic contrast enhanced MRI datasets. Med Image Comput Comput Assist Interv 2007;10:261-9.
38. van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 2000;27:261-3.
39. Bruynesteyn K, Boers M, Kostense P, et al. Deciding on progression of joint damage in paired films of individual patients: smallest detectable difference or change. Ann Rheum Dis 2005;64:179-82.
40. Haavardsholm EA, Bøyesen P, Østergaard M, et al. MRI-detected bone marrow edema is a predictor of subsequent radiographic progression in early rheumatoid arthritis [abstract]. Ann Rheum Dis 2007;66(Suppl 2):94.