H.H. Kuper

The efficacy of anti‐TNF in rheumatoid arthritis, a comparison between randomised controlled trials and clinical practice

Background: Randomised controlled trials (RCTs) evaluating the efficacy of antagonists to tumour necrosis factor α (TNFα) showed high response percentages in the groups treated with active drugs. Objective: To compare the efficacy of anti-TNF treatments for rheumatoid arthritis (RA) patients in RCTs and in daily clinical practice, with an emphasis on the efficacy for patients eligible and not eligible for RCTs of anti-TNF treatments. Methods: First, randomised placebo-controlled trials written in English for etanercept, infliximab and adalimumab for patients with RA were selected by a systematic review. Second, the DREAM (Dutch Rheumatoid Arthritis Monitoring) register with patients starting for the first time on one of the TNF-blocking agents was used. Patient characteristics, doses of medication and co-medication as well as the ACR20 response percentages were compared between RCTs and DREAM data, stratified for trial eligibility. Results: In 10 of 11 comparisons, the ACR20 response percentages were lower in daily clinical practice than in the RCT active drug group, which was significant in five of 11 comparisons. Only 34–79% of DREAM patients fulfilled the selection criteria for disease activity in the several RCTs examined. DREAM patients eligible for RCTs had higher response percentages than ineligible DREAM patients. ACR20 response percentages of eligible DREAM patients were comparable with the ACR20 response percentages of the RCT active drug group in 10 of 11 comparisons. Conclusion: The efficacy of TNF-blocking agents in RCTs exceeded the efficacy of these drugs in clinical practice. However, in clinical practice more patients with lower disease activity were treated with TNF-blocking agents compared with those treated in RCTs. For daily practice patients who were eligible for RCTs, responses were more similar to responses reached in RCTs.

The effectiveness and medication costs of three anti-tumour necrosis factor alpha agents in the treatment of rheumatoid arthritis from prospective clinical practice data.

AIM to evaluate the effects of adalimumab, etanercept and infliximab on disease activity, functional ability and quality of life and the medication costs in a naturalistic design. METHODS All patients from the Dutch Rheumatoid Arthritis Monitoring (DREAM) register starting on tumour necrosis factor (TNF)alpha-blocking agents for the first time were monitored and assessed by trained research nurses every 3 months. The primary outcome was the Disease Activity Score (DAS28) course over the 12 months follow-up, analysed by linear mixed models. Secondary outcomes were the Health Assessment Questionnaire (HAQ), EuroQol five dimensions (EQ-5D) and the Short-Form 36 items (SF36) scores, and medication-related total costs. RESULTS The DAS28 and SF-36 physical component scale decreased in all three medication groups over 12 months, but the decrease was larger for adalimumab and etanercept in comparison to infliximab (p<0.001). The analyses of the HAQ and the EQ-5D scores showed the same (non-significant) trend, namely that at 12 months, the functionality and quality of life was better for adalimumab and etanercept patients. With regard to the medication costs, infliximab treatment resulted in significantly higher costs over the follow-up period than treatments with either adalimumab or etanercept. The comparison between adalimumab and etanercept showed a significant difference in the 12-month DAS28 course (p = 0.031). There were no additional indications for differences in effectiveness or costs between adalimumab and etanercept. CONCLUSION The evaluation of the effectiveness and costs showed that adalimumab and etanercept are more or less equal and favourable compared to infliximab in the first year of treatment.

A tight control treatment strategy aiming for remission in early rheumatoid arthritis is more effective than usual care treatment in daily clinical practice: a study of two cohorts in the Dutch Rheumatoid Arthritis Monitoring registry

There is strong evidence from clinical trials that a ‘treat to target’ strategy is effective in reaching remission in rheumatoid arthritis (RA). However, the question is whether these results can be translated into daily clinical practice and clinical remission is a reachable target indeed. Objective The study aims to investigate whether in early RA a treatment strategy aiming at Disease Activity Score (DAS) 28 <2.6 is more effective than ‘usual care’ treatment for reaching clinical remission after 1 year. Methods Two early RA inception cohorts from two different regions including patients who fulfilled the American College of Rheumatology criteria for RA were compared. Patients in the tight-control cohort (n=126) were treated according to a DAS28-driven step-up treatment strategy starting with methotrexate, addition of sulphasalazine (SSZ) and exchange of SSZ by anti-tumour necrosis factor in case of failure. Patients in the usual-care cohort (n=126) were treated with methotrexate or SSZ, without DAS28-guided treatment decisions. The primary outcome was the percentage remission (DAS28<2.6) at 1 year. Time to first remission and change in DAS28 were secondary outcomes. Results After 1 year, 55% of tight-control patients had a DAS28<2.6 versus 30% of usual care patients (OR 3.1, 95% CI 1.8 to 5.2). The median time to first remission was 25 weeks for tight control and more than 52 weeks for usual care (p<0.0001). The DAS28 decreased with −2.5 in tight control and −1.5 in usual care (p<0.0001). Conclusion In early RA, a tight control treatment strategy aiming for remission leads to more rapid DAS28 remission and higher percentages of remission after 1 year than does a usual care treatment.

The effectiveness and medication costs of three anti-TNF agentsα in the treatment of rheumatoid arthritis from prospective clinical practice data

AIM to evaluate the effects of adalimumab, etanercept and infliximab on disease activity, functional ability and quality of life and the medication costs in a naturalistic design. METHODS All patients from the Dutch Rheumatoid Arthritis Monitoring (DREAM) register starting on tumour necrosis factor (TNF)alpha-blocking agents for the first time were monitored and assessed by trained research nurses every 3 months. The primary outcome was the Disease Activity Score (DAS28) course over the 12 months follow-up, analysed by linear mixed models. Secondary outcomes were the Health Assessment Questionnaire (HAQ), EuroQol five dimensions (EQ-5D) and the Short-Form 36 items (SF36) scores, and medication-related total costs. RESULTS The DAS28 and SF-36 physical component scale decreased in all three medication groups over 12 months, but the decrease was larger for adalimumab and etanercept in comparison to infliximab (p<0.001). The analyses of the HAQ and the EQ-5D scores showed the same (non-significant) trend, namely that at 12 months, the functionality and quality of life was better for adalimumab and etanercept patients. With regard to the medication costs, infliximab treatment resulted in significantly higher costs over the follow-up period than treatments with either adalimumab or etanercept. The comparison between adalimumab and etanercept showed a significant difference in the 12-month DAS28 course (p = 0.031). There were no additional indications for differences in effectiveness or costs between adalimumab and etanercept. CONCLUSION The evaluation of the effectiveness and costs showed that adalimumab and etanercept are more or less equal and favourable compared to infliximab in the first year of treatment.

Sustained beneficial effects of a protocolized treat-to-target strategy in very early rheumatoid arthritis: three-year results of the Dutch Rheumatoid Arthritis Monitoring remission induction cohort.

Treat‐to‐target (T2T) leads to improved clinical outcomes in early rheumatoid arthritis (RA). The question is whether these results sustain in the long term. Our objective was to investigate the 3‐year results of a protocolized T2T strategy in daily clinical practice.

Treating to the target of remission in early rheumatoid arthritis is cost-effective: results of the DREAM registry.

BackgroundWhere health economic studies are frequently performed using modelling, with input from randomized controlled trials and best guesses, we used real-life data to analyse the cost-effectiveness and cost-utility of a treatment strategy aiming to the target of remission compared to usual care in early rheumatoid arthritis (RA).MethodsWe used real-life data from comparable cohorts in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry: the DREAM remission induction cohort (treat-to-target, T2T) and the Nijmegen early RA inception cohort (usual care, UC). Both cohorts were followed prospectively using the DREAM registry methodology. All patients fulfilled the American College of Rheumatology criteria for RA and were included in the cohort at the time of diagnosis. The T2T cohort was treated according to a protocolised strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6). The UC cohort was treated without DAS28-guided treatment decisions. EuroQol-5D utility scores were estimated from the Health Assessment Questionnaire. A health care perspective was adopted and direct medical costs were collected. The incremental cost effectiveness ratio (ICER) per patient in remission and incremental cost utility ratio (ICUR) per quality-adjusted life year (QALY) gained were calculated over two and three years of follow-up.ResultsTwo year data were available for 261 T2T patients and 213 UC patients; an extended follow-up of three years was available for 127 and 180 patients, respectively. T2T produced higher remission percentages and a larger gain in QALYs than UC. The ICER was € 3,591 per patient in remission after two years and T2T was dominant after three years. The ICUR was € 19,410 per QALY after two years and T2T was dominant after three years.ConclusionsWe can conclude that treating to the target of remission in early RA is cost-effective compared with UC. The data suggest that in the third year, T2T becomes cost-saving.

Frequency and effectiveness of dose increase of adalimumab, etanercept, and infliximab in daily clinical practice

To describe the frequency and effectiveness of dose increase of adalimumab, etanercept, and infliximab in the treatment of rheumatoid arthritis (RA) in daily clinical practice.

Evaluating guidelines on continuation of anti-tumour necrosis factor treatment after 3 months: clinical effectiveness and costs of observed care and different alternative strategies

Objective: To study the adherence of rheumatologists to the Dutch guidelines for anti-tumour necrosis factor alpha (TNF-α) treatment. The secondary objective was to evaluate alternatives to the present guidelines with regard to the percentage of responders and costs. Methods: The response (>1.2 DAS28 decrease) in patients who started on anti-TNF-α treatment for the first time was evaluated at 3 and 6 months after initiation. How many patients continued or discontinued their initial anti-TNF-α treatment was evaluated. Possible alternative guidelines were evaluated by means of a decision tree, with regard to the expected percentage of successfully (responders) and unsuccessfully treated patients and expected costs. Results: At 3 months 56% (N  =  306) and 44% (N  =  233) of all 539 evaluable patients were classified as responders or non-responders, respectively. Despite the guidelines, most (81%) (N  =  189) of the non-responders continued treatment. 37% of the non-responders who continued anti-TNF-α treatment were eventually classified as responders at 6 months. Decision analytical modelling showed that with equal expected costs all alternative strategies would result in more responders than according to theoretical full adherence with the guidelines. “Continuation in case of partial response” had the best trade-off between successfully treated patients (64%) and unsuccessfully treated patients (17%). Conclusion: There was suboptimal adherence to the Dutch guidelines for treatment with anti-TNF-α for rheumatoid arthritis patients. This seemed to be justified by the fact that a delayed response up to 6 months was shown. If treatment is continued despite a non-response at 3 months, this is only recommended in patients with at least a partial response (at least 0.6 DAS28 improvement).

THU0118 General Applicability of a New Treat-to-Target Treatment Strategy in Dutch Patients with Early Rheumatoid Arthritis: Results from the Dream Remission induction Cohort II

Background New treatment options and strategies have dramatically reduced the severity and impact of rheumatoid arthritis (RA) and especially early intensive combination therapy, aimed at achieving remission, has shown good clinical outcomes. The reason for early identification and treatment of RA is to control progression of the disease. Since there is no cure for RA, the current most important goal is to reach remission as soon as possible, which should be sustained during the course of the disease. Objectives Despite wide implementation of treat-to-target (T2T) strategies in RA, a proportion of patients still fail to achieve early remission. This study aimed to identify baseline predictors of reaching remission in Dutch patients with early RA following a T2T strategy. Methods Baseline demographic, clinical and patient-reported outcome measures and one-year follow-up data were used from patients with early RA included in the DREAM remission induction cohort II study. Survival analyses and simple and multivariable logistic regression analyses were used to examine remission rates and significant predictors of achieving remission. Results A total number of 137 patients was included. 77.2% of the patients reached remission at least once in 12 months follow-up, and median time to first remission was 17 weeks. None of the examined baseline variables were significantly associated with achieving remission within 1 year. Lower ESR (p=0.007), male gender (p=0.057), better physical health status (p=0.062) and fewer tender joints (p=0.175) were significantly or marginally associated with achieving remission within 17 weeks. In multivariable analysis, however, only ESR remained significantly predictive (p=0.023). Conclusions The results indicate that baseline characteristics were not predictive of early remission. Together with the high proportion of responders, this provides additional evidence for the general applicability of T2T strategies in patients with early RA. Disclosure of Interest None declared