Rheumatoid Arthritis: van Tuyl LH

van Tuyl LH, Vlad SC, Felson DT, Wells G, Boers M. · VU University Medical Center, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #19405006 No free full text.

Abstract: OBJECTIVE: Due to advances in rheumatoid arthritis (RA) therapies over the last few years, an increasing proportion of patients are able to achieve a state of remission. However, the definition of remission is unclear. Currently, randomized controlled trials around the world use different remission definitions and consequently measure different aspects of a patient's disease state. The need for a uniform definition of remission is vital for research findings to be correctly interpreted. METHODS: The American College of Rheumatology (ACR) constituted a committee that included international clinical researchers, trialists, and clinical epidemiologists in order to redefine remission in RA. This group was asked to study current definitions of remission, explore the theoretical underpinning of the concept of remission, and develop a research agenda that would inform future work in the development of an ACR definition of remission. RESULTS: In its first meeting, the committee preferred to develop a strict definition, implying no or very low disease activity. Such a definition would need to be validated against long-term outcome, e.g., physical function and damage. CONCLUSION: The committee decided to consider both a definition for trials and a modified version for clinical practice. Since the first meeting, the ACR and the European League Against Rheumatism (EULAR) have decided to sponsor this initiative as an official ACR/EULAR collaboration.

van Tuyl LH, Lems WF, Voskuyl AE, Kerstens PJ, Garnero P, Dijkmans BA, Boers M. · Department of Clinical Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. · Ann Rheum Dis. · Pubmed #18625629 No free full text.

Abstract: OBJECTIVE: To investigate the efficacy and feasibility of an intensive combination treatment in early rheumatoid arthritis (RA) combined with monitoring both disease activity and cartilage degradation. METHODS: In a pilot trial, 21 patients with active early RA (mean DAS28 5.3; mean disease duration 3 months) were treated with COBRA treatment comprising sulfasalazine, methotrexate and high-dose step-down prednisolone, intensified by adding hydroxychloroquine and continued low-dose prednisolone. In addition, based on measurements of disease activity or a marker of cartilage degradation (CTX-II), treatment adjustments were possible with methotrexate intensification after 8 or 21 weeks; and with infliximab after 21 weeks. RESULTS: Nineteen of 21 patients (90%) were in remission (DAS28 <2.6) after 40 weeks (8 weeks, 57%; 21 weeks, 76%). American College of Rheumatology (ACR) criteria, ACR20, 50, 70 and 90 improvements rates were 100%, 95%, 71% and 43% respectively. CTX-II excretion decreased by mean (SD) 347(292) ng/mmol creatinine, but only 50% of patients reduced their CTX-II excretion below the cut-off point. The two monitoring groups showed no significant difference in remission according to DAS score or CTX-II excretion, despite a trend towards more intensive treatment in the CTX-II group. Treatment intensification was feasible according to protocol. CONCLUSIONS: This small pilot study suggests that intensified and tightly controlled COBRA treatment is uniquely effective in early RA. TRIAL REGISTRATION NUMBER: ISRCTN96372677.

van Tuyl LH, Plass AM, Lems WF, Voskuyl AE, Kerstens PJ, Dijkmans BA, Boers M. · Department of Rheumatology, EMGO Institute, and the Department of Epidemiology and Biostatistics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands. · J Rheumatol. · Pubmed #19487259 No free full text.

Abstract: OBJECTIVE: COBRA combination therapy is well known and has uncontested efficacy in the treatment of rheumatoid arthritis (RA). However, it is infrequently applied in Dutch clinical practice. Based on qualitative research on opinions of physicians and patients towards COBRA therapy, our study describes the development and pilot testing of an implementation package to facilitate prescription and use of COBRA therapy in early RA. METHODS: The implementation package was developed to address specific barriers towards prescription of COBRA therapy and comprised informational handouts (an information booklet and leaflet for patients), preprinted prescription orders, and background information on COBRA therapy for the rheumatologists. Twenty-two rheumatologists agreed to participate, including the arthritis nurse where available. Rheumatologists, nurses, and patients were asked to record their experience. All Dutch arthritis nurses were invited to an educational session on COBRA therapy. RESULTS: Sixteen rheumatologists accompanied by 10 arthritis nurses used the material to prescribe COBRA therapy to a total of 27 patients. Rheumatologists and nurses both gave high marks to the supplied materials. Eighty-eight percent of rheumatologists reported that the material sped up the prescription process, and 65% indicated they would prescribe COBRA therapy more frequently if these materials were available routinely. Patients expressed great satisfaction with the information handouts, rating it 2.8 (standard deviation 0.5) on a scale of -3 (very negative) to +3 (very positive). Most patients (89%) planned to keep the information booklet as a reference and 70% used it as a tool to remember the correct intake of medication. The attitude and perceived capability of nurses towards the guidance of patients with RA receiving COBRA therapy was improved through a brief educational intervention. CONCLUSION: Rheumatologists, patients, and arthritis nurses all highly appreciated the implementation package and indicated that its availability would increase uptake of COBRA therapy.

van Tuyl LH, Plass AM, Lems WF, Voskuyl AE, Kerstens PJ, Dijkmans BA, Boers M. · Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. · Rheumatology (Oxford). · Pubmed #18710900 No free full text.

Abstract: OBJECTIVE: The COBRA therapy (combination therapy in early rheumatoid arthritis) has proven to be an effective treatment for early RA, but is rarely prescribed. A survey showed reluctance of Dutch reumatologists to apply COBRA therapy in early RA. The present qualitative study was carried out to further explore the reservation of Dutch rheumatologists towards prescribing COBRA therapy and include patients' view on (components of) COBRA therapy. METHODS: Two focus group discussions were undertaken for rheumatologists (n(1) = 8, n(2) = 7) and two for patients (n(1) = 4, n(2) = 8). In addition, in-depth interviews were conducted with 11 rheumatologists and 1 patient. These were taped and transcribed. Two independent researchers identified themes and these were discussed with three other researchers. RESULTS: Rheumatologists were positive concerning effectiveness of COBRA therapy, but highly concerned about their patients' possible negative reaction to the large amount of pills to be prescribed. In addition, rheumatologists perceived lack of time explaining and prescribing COBRA therapy and felt uncomfortable prescribing high doses of prednisolone. Patients were positive about an aggressive combination therapy such as COBRA, and they had no qualms taking many pills if this could improve their prognosis. Patients associated prednisolone with negative side-effects, but were also aware of the benefits and the need of prednisolone in rough times. A decrease in the amount of pills after intensive treatment was highly appreciated. CONCLUSION: Rheumatologists and patients differed in opinion about the use of COBRA therapy. Rheumatologists were particularly concerned about their patients' reaction towards them prescribing such an aggressive and complex therapy, whereas patients, while aware of the side-effects, were most interested in suppressing illness symptoms and reducing future damage regardless of the amount of pills.

van Tuyl LH, Plass AM, Lems WF, Voskuyl AE, Dijkmans BA, Boers M. · Department of Clinical Epidemiology & Biostatistics, VU University Medical Center, PO Box 7057, 1053 MB Amsterdam, The Netherlands. · Ann Rheum Dis. · Pubmed #17392349 No free full text.

Abstract: BACKGROUND: The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial has proved that combination therapy with prednisolone, methotrexate and sulphasalazine is superior to sulphasalazine monotherapy in suppressing disease activity and radiological progression of early rheumatoid arthritis (RA). In addition, 5 years of follow-up proved that COBRA therapy results in sustained reduction of the rate of radiological progression. Despite this evidence, Dutch rheumatologists seem reluctant to prescribe COBRA therapy. OBJECTIVE: To explore the reasons for the reluctance in Dutch rheumatologists to prescribe COBRA therapy. METHODS: A short structured questionnaire based on social-psychological theories of behaviour was sent to all Dutch rheumatologists (n = 230). RESULTS: The response rate was 50%. COBRA therapy was perceived as both effective and safe, but complex to administer. Furthermore, rheumatologists expressed their concern about the large number of pills that had to be taken, the side effects of high-dose prednisolone and the low dose of methotrexate. Although the average attitude towards the COBRA therapy was slightly positive (above the neutral point), the majority of responding rheumatologists had a negative intention (below the neutral point) to prescribe COBRA therapy in the near future. CONCLUSION: The reluctance of Dutch rheumatologists to prescribe effective COBRA therapy may be due to perceptions of complexity of the treatment schedule and negative patient-related consequences of the therapy.

van Tuyl LH, Lems WF, Voskuyl AE, Dijkmans BA, Boers M, Kerstens PJ. · No affiliation provided · Arthritis Rheum. · Pubmed #19116962 No free full text.

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