Mart A F J van de Laar

Long-term effectiveness and safety of TNF-blocking agents in daily clinical practice: results from the Dutch Rheumatoid Arthritis Monitoring register

OBJECTIVESnExperience with anti-TNF agents for a decade can be used to research the safety and effectiveness of anti-TNF agents in the long term. The objective of this article is to describe drug survival, disease activity, daily functioning, quality of life and adverse events of TNF-blocking agents in daily clinical practice after 5 years of follow-up.nnnMETHODSnData from the Dutch Rheumatoid Arthritis Monitoring (DREAM) register of 1560 RA patients were used for analyses (5-year follow-up, n=174). Drug survival and time to first serious infection or malignancy were analysed by Kaplan-Meier analysis. Several outcome measures at several follow-up moments were analysed per intention to treat and per protocol.nnnRESULTSnThe 5-year drug survival of the first anti-TNF was 45%, and 60% for total use of TNF-blocking agents. Baseline 28-joint DAS (DAS-28) was 5.1 (s.d. 1.3). After 5 years, the mean DAS-28 was 3.2 (s.d. 1.3) in all patients who had started with TNF-blocking agents and 2.9 (s.d. 1.1) in patients who were still on TNF-blocking agents. In the latter group, the HAQ score was 0.88 (s.d. 0.7) and the EuroQol five dimensions (EQ-5D) utility score was 0.7 (s.d. 0.2). Incidence rates of serious infections and malignancies were 2.9 and 0.6 per 100 patient-years, respectively.nnnCONCLUSIONnFive-year follow-up of RA patients treated with TNF-blocking agents showed a 60% drug survival accompanied by sustained low disease activity, normalized function and quality of life similar to that in the general population. The benefit to risk ratio for long-term TNF-blocking therapy remains favourable.

The prevalence of clinical remission in RA patients treated with anti-TNF: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry

OBJECTIVESnTo evaluate the prevalence of clinical remission and minimal disease activity according to the ACR/European League Against Rheumatism (EULAR) remission, DAS-28 <2.6 and minimal disease activity (MDA) criteria, and to compare the extent of residual disease activity with disability in RA patients after 6 months of treatment with anti-TNF.nnnMETHODSnIn the Dutch Rheumatoid Arthritis Monitoring (DREAM) biologic registry the prevalence of DAS-28 <2.6, MDA and ACR/EULAR remission criteria was assessed. Residual disease activity during MDA or remission was assessed as the percentage of patients with swollen and tender joints, elevated acute-phase reactants and general health on a visual analogue scale (VAS). Disability was evaluated with the HAQ score.nnnRESULTSnPrevalence of DAS-28 <2.6 was 27%, prevalence of MDA was 34% and ACR/EULAR remission was reached by 6% of patients. Residual disease activity was present mostly in the most lenient criteria and occurred most frequently on the level of swollen joint count and VAS score: at least one swollen joint in DAS-28 <2.6, MDA and ACR/EULAR remission was present in, respectively, 51, 54 and 34% of the patients. VAS >1 occurred in, respectively, 67, 69 and 0% of the patients. Modification of the cut-point of the patient-reported outcome increased the prevalence of ACR/EULAR remission, but also the level of disability.nnnCONCLUSIONnMDA and DAS-28 <2.6 are reachable treatment targets in RA with anti-TNF, although residual disease activity might still be present. In turn, ACR/EULAR remission criteria leave little residual disease activity, but might be too stringent for use in daily clinical practice due to the strict cut-point in the patient-reported outcome.

The provisional ACR/EULAR definition of remission in RA : a comment on the patient global assessment criterion

OBJECTIVESnThe provisional ACR/European League Against Rheumatism (EULAR) definition of remission in RA requires a score of ≤1 on the patient global assessment (PGA, 0-10 scale). We explored the relation between the PGA criterion and the patients clinical disease state in an observational dataset.nnnMETHODSnData of 512 newly diagnosed RA patients of the Dutch Rheumatoid Arthritis Monitoring (DREAM) remission induction cohort were analysed. Both 28-joint counts and more comprehensive joint counts (tender joint count-53, swollen joint count-44) were used.nnnRESULTSnACR/EULAR remission was present in 20.1% of the patients when using 28-joint counts and in 17.4% of the patients when applying more comprehensive joint counts. In 108 patients, the PGA score was >1 despite fulfilment of the remaining criteria (TJC28, SJC28 and CRP in mg/dl ≤1). Residual disease activity was observed in 31.5% (34/108) and median (interquartile range) scores on PGA, pain and fatigue were 2.4 (1.8-4.0), 2.0 (1.1-3.0) and 2.7 (1.3-5.0), respectively. Applying more comprehensive joint counts showed comparable results. In 19.5% (100/512) of patients, disease activity was absent (TJC53u2009=u20090, SJC44u2009=u20090, and CRP ≤1). In 41% (nu2009=u200941) of these patients, the PGA score was >1. Receiver operating characteristic analysis showed moderate accuracy of the PGA to discriminate between fulfilment and no fulfilment of all remaining criteria.nnnCONCLUSIONnFrequently, patients did not meet the PGA criterion despite a good clinical disease state. Apparently the PGA is not solely influenced by RA disease activity. In patients with marked divergence between the PGA and objective clinical measurements, caution should be taken when applying the provisional ACR/EULAR definition of remission.

The patient-therapist relationship as an indicator for treatment success in e-health treatments for patients with rheumatoid arthritis and psorias.

Background The popularity of E-health is rising and research has shown that E-health interventions can be effective [1]. However, they also offer new challenges and questions in clinical practice and research, for example about the role of the patient-therapist relationship [2,3]. In face-to-face treatments, a better patient-therapist relationship has often been reported as a predictor for improved treatment outcome. Objectives In an E-health cognitive-behavioral treatment for patients with rheumatoid arthritis and psoriasis, the patient-therapist relationship was assessed and related to patient-reported outcomes. Methods After a face-to-face intake, all patient-therapist contact was through e-mail. Patients rated the patient-therapist relationship pre and post treatment using the Working Alliance Inventory and internet-specific relationship questions. After treatment, patients were asked to rate improvement in symptoms and coping with these symptoms. Paired samples t-tests (patient-therapist relationship change during treatment) and regression analyses (association patient-therapist relationship and patient-reported outcome) were performed in a subsample of patients who had finished treatment. Results The patient-therapist relationship was rated positively and increased during treatment (p <.05) as generally found in face to face treatments. Both a better patient-therapist relationship and the specific internet related aspects (e.g., having time to think about the reply to the therapist) predicted patient-reported improvement in coping with disease problems, such as pain and fatigue (p-values <.05). At the end of treatment both relationship aspects are related to improvements in symptoms and coping with these symptoms (all p-values <.05). Conclusions These preliminary results indicate that the patient-therapist relationship is a possible predictor for self-reported improvements in E-health treatments, similar to the role of this patient-therapist relationship in face-to-face treatments. Future results need to demonstrate whether the patient-therapist relationship also contributes to the cost-effectiveness of this E-health treatment in the randomized controlled trial. References Cuijpers, P., Straten, A., & Andersson, G. Internet-administered cognitive behavior therapy for health problems: A systematic review. Journal of Behavioral Medicine 2008;31:169-77. Martin, D.J., Garske, J.P., & Davis, M.K. Relation of the therapeutic alliance with outcome and other variables: A meta-analytic review. Journal of Counseling and Clinical Psychology 2000;68:438-50. Preschl, B., Maercker, A., & Wagner, B. The working alliance in a randomized control trial comparing online with face-to-face cognitive behavioral therapy for depression. BMC Psychiatry 2011;11:189. Acknowledgements We would like to thank the patient representatives Henk van Duijn, Mariëtte Tomas, and Hen Ros for their contributions to the study, and ZonMw (The Netherlands Organisation for Health Research and Development) and Pfizer Inc. for their financial contribution to this research project. Disclosure of Interest M. Ferwerda Grant/research support from: Pfizer Inc., S. Spillekom: None Declared, H. van Middendorp: None Declared, S. van Beugen Grant/research support from: Pfizer Inc., W. Kievit: None Declared, J. Fransen: None Declared, H. Visser: None Declared, P. van Oijen: None Declared, E. Taal: None Declared, P. van Riel Consultant for: Roche, Abbott, Pfizer, E. de Jong: None Declared, P. van de Kerkhof: None Declared, M. van der Laar: None Declared, A. Evers Grant/research support from: Pfizer Inc., Consultant for: Roche