Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped?

被引:164
作者
Saleem, Benazir [1 ]
Keen, Helen [1 ]
Goeb, Vincent [1 ]
Parmar, Rekha [1 ]
Nizam, Sharmin [1 ]
Hensor, Elizabeth M. A. [1 ]
Churchman, Sarah M. [1 ]
Quinn, Mark [1 ]
Wakefield, Richard [1 ]
Conaghan, Philip G. [1 ]
Ponchel, Frederique [1 ]
Emery, Paul [1 ]
机构
[1] Univ Leeds, Sect Musculoskeletal Dis, Leeds Inst Mol Med, Leeds LS7 4SA, W Yorkshire, England
关键词
EARLY RHEUMATOID-ARTHRITIS; DIFFERENT TREATMENT STRATEGIES; ADALIMUMAB PLUS METHOTREXATE; ACTIVATED T-CELLS; DOUBLE-BLIND; CLINICAL REMISSION; DELAYED TREATMENT; DISEASE-ACTIVITY; CONTROLLED-TRIAL; COMBINATION;
D O I
10.1136/ard.2009.117341
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Objectives Combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockade has increased remission rates in patients with rheumatoid arthritis. However, there are no guidelines regarding cessation of therapy. There is a need for markers predictive of sustained remission following cessation of TNF blocker therapy. Methods Patients in remission (DAS28 <2.6) treated with a TNF blocker and MTX as initial or delayed therapy were recruited. Joints were assessed for grey scale synovitis and power Doppler (PD) activity. Immunological assessment involved advanced six-colour flow cytometry. Results Of the 47 patients recruited, 27 had received initial treatment and 20 delayed treatment with TNF blocking drugs. Two years after stopping TNF blocker therapy, the main predictor of successful cessation was timing of treatment; 59% of patients in the initial treatment group sustained remission compared with 15% in the delayed treatment group (p=0.003). Within the initial treatment group, secondary analysis showed that the only clinical predictor of successful cessation of treatment was shorter symptom duration before receiving treatment (median 5.5 months vs 9 months; p=0.008). No other clinical features were associated with successful cessation of therapy. Thirty-five per cent of patients had low PD activity but levels were not informative. Several immunological parameters were significantly associated with sustained remission including abnormal differentiation subset of T cells and regulatory T cells. Similar non-significant trends were observed in the delayed treatment group. Conclusion In patients in remission with low levels of imaging synovitis receiving combination treatment with a TNF blocker and MTX, immunological parameters and short duration of untreated symptoms were associated with successful cessation of TNF blocker therapy.
引用
收藏
页码:1636 / 1642
页数:7
相关论文
共 33 条
[1]
The PREMIER study - A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment [J].
Breedveld, FC ;
Weisman, MH ;
Kavanaugh, AF ;
Cohen, SB ;
Pavelka, K ;
van Vollenhoven, R ;
Sharp, J ;
Perez, JL ;
Spencer-Green, GT .
ARTHRITIS AND RHEUMATISM, 2006, 54 (01) :26-37
[2]
Effect of discontinuing TNFα antagonist therapy in patients with remission of rheumatoid arthritis [J].
Brocq, Olivier ;
Millasseau, Elodie ;
Albert, Christine ;
Grisot, Christian ;
Flory, Philippe ;
Roux, Christian-Hubert ;
Euller-Ziegler, Liana .
JOINT BONE SPINE, 2009, 76 (04) :350-355
[3]
An Explanation for the Apparent Dissociation Between Clinical Remission and Continued Structural Deterioration in Rheumatoid Arthritis [J].
Brown, A. K. ;
Conaghan, P. G. ;
Karim, Z. ;
Quinn, M. A. ;
Ikeda, K. ;
Peterfy, C. G. ;
Hensor, E. ;
Wakefield, R. J. ;
O'Connor, P. J. ;
Emery, P. .
ARTHRITIS AND RHEUMATISM, 2008, 58 (10) :2958-2967
[4]
Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission - Evidence from an imaging study may explain structural progression [J].
Brown, A. K. ;
Quinn, M. A. ;
Karim, Z. ;
Conaghan, P. G. ;
Peterfy, C. G. ;
Hensor, E. ;
Wakefield, R. J. ;
O'Connor, P. J. ;
Emery, P. .
ARTHRITIS AND RHEUMATISM, 2006, 54 (12) :3761-3773
[5]
C-reactive protein as a predictor of infliximab treatment outcome in patients with rheumatoid arthritis - Defining subtypes of nonresponse and subsequent response to etanercept [J].
Buch, MH ;
Seto, Y ;
Bingham, SJ ;
Bejarano, V ;
Bryer, D ;
White, J ;
Emery, P .
ARTHRITIS AND RHEUMATISM, 2005, 52 (01) :42-48
[6]
Abnormal T cell differentiation persists in patients with rheumatoid arthritis in clinical remission and predicts relapse [J].
Burgoyne, C. H. ;
Field, S. L. ;
Brown, A. K. ;
Hensor, E. M. ;
English, A. ;
Bingham, S. L. ;
Verburg, R. ;
Fearon, U. ;
Lawson, C. A. ;
Hamlin, P. J. ;
Straszynski, L. ;
Veale, D. ;
Conaghan, P. ;
Hull, M. A. ;
van Laar, J. M. ;
Tennant, A. ;
Emery, P. ;
Isaacs, J. D. ;
Ponchel, F. .
ANNALS OF THE RHEUMATIC DISEASES, 2008, 67 (06) :750-757
[7]
EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT) [J].
Combe, B. ;
Landewe, R. ;
Lukas, C. ;
Bolosiu, H. D. ;
Breedveld, F. ;
Dougados, M. ;
Emery, P. ;
Ferraccioli, G. ;
Hazes, J. M. W. ;
Klareskog, L. ;
Machold, K. ;
Martin-Mola, E. ;
Nielsen, H. ;
Silman, A. ;
Smolen, J. ;
Yazici, H. .
ANNALS OF THE RHEUMATIC DISEASES, 2007, 66 (01) :34-45
[8]
Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFα therapy [J].
Ehrenstein, MR ;
Evans, JG ;
Singh, A ;
Moore, S ;
Warnes, G ;
Isenberg, DA ;
Mauri, C .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (03) :277-285
[9]
Clinical identification and treatment of a rapidly progressing disease state in patients with rheumatoid arthritis [J].
Emery, P. ;
McInnes, I. B. ;
van Vollenhoven, R. ;
Kraan, M. C. .
RHEUMATOLOGY, 2008, 47 (04) :392-398
[10]
EARLY RHEUMATOID-ARTHRITIS - TIME TO AIM FOR REMISSION [J].
EMERY, P ;
SALMON, M .
ANNALS OF THE RHEUMATIC DISEASES, 1995, 54 (12) :944-947