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.

UNLABELLED: 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.

Treatment strategies aiming at remission in early rheumatoid arthritis patients: starting with methotrexate monotherapy is cost-effective.

OBJECTIVE: To perform a modelling study on the cost-effectiveness of three outcome-directed strategies in early RA patients: Strategy 1: starting MTX monotherapy, followed by the addition of LEF, followed by MTX with addition of anti-TNF; Strategy 2: start with MTX and LEF combination followed by MTX with anti-TNF; and Strategy 3: immediate start with MTX and anti-TNF. METHODS: A validated Markov model was used to evaluate the cost-effectiveness of the three strategies. Effectiveness of the strategies was determined using daily practice data from two cohorts and used as input parameter in the model. Patients treated according to the strategies were matched for baseline 28-joint DAS (DAS-28). Using Monte Carlo simulation, expected costs, quality-adjusted life-years (QALYs) and incremental cost per QALY gained for a 5-year time horizon were calculated following both a health-care and a societal perspective. RESULTS: The percentage of patients in remission and number of QALYs were comparable between the three strategies. Starting with a combination (MTX plus LEF or anti-TNF) was more costly than starting with MTX alone. This resulted in an unfavourable incremental cost-effectiveness ratio for starting on anti-TNF vs initially MTX: health-care perspective of €138,028 and from a societal perspective of €136,150 per QALY gained over 5 years. CONCLUSION: In this modelling study, starting with MTX or anti-TNF has comparable effectiveness. However, initial anti-TNF was far more expensive than starting with MTX monotherapy. Therefore, based on this study, a treatment strategy starting with MTX monotherapy is favoured over a strategy with MTX and anti-TNF right away in early RA patients.

Meta-analysis of tight control strategies in rheumatoid arthritis: protocolized treatment has additional value with respect to the clinical outcome.

OBJECTIVES: Tight control studies including regular assessments of disease activity have shown that this approach has beneficial effects on disease activity, disability and joint damage in treating RA patients. Some of these studies included tight control with protocolized treatment, while others applied tight control without protocolized treatment. The aim of this study was to compare the effects of tight control with usual care and to compare the effects of tight control studies with and without protocolized treatment adjustments. METHODS: A systematic literature search was performed to identify clinical trials in RA that evaluated tight control strategies in comparison with usual care. Two types of study were compared: (i) those using disease activity monitoring with protocolized treatment adjustments, and (ii) those using disease activity monitoring without protocolized treatment adjustments. The databases PubMed and Cochrane were searched from 1995 up to 2009. Primary outcome measure was the mean change in the 28-joint DAS (DAS-28), which was used in a random-effects meta-analysis. RESULTS: Six controlled trials regarding tight control in RA patients were included in the meta-analysis. In all trials, patients treated in the tight control arms had significantly higher DAS-28 responses than patients treated according to usual care [weighted mean difference (WMD) = 0.59, P < 0.001]. Moreover, tight control was significantly more effective (P < 0.001) by means of protocolized treatment adjustments (WMD = 0.97) compared with non-protocolized monitoring of disease activity (WMD = 0.25). CONCLUSION: Tight control in RA resulted in significantly better clinical outcomes than usual care. It is suggested but not proved that tight control with protocolized treatment adjustments is more beneficial than if no such protocol is used.

Methotrexate in combination with sulfasalazine is more effective in rheumatoid arthritis patients who failed sulfasalazine than in patients naive to both drugs.

OBJECTIVES: For pharmacological reasons, the effect of the combination of MTX and SSZ may be different in RA patients who are naïve to these drugs compared to patients with an insufficient response to one of them. Therefore, we compared the results of randomized controlled trials (RCTs) on the combination of MTX and SSZ in naïve patients and in patients with an insufficient response to SSZ. METHODS: A systematic literature search was performed to identify RCTs that compared the MTX-SSZ combination to either drug alone. The databases MEDLINE and the Cochrane Clinical Trials registry were searched from 1966 up to April 2007. The efficacy of the single therapeutic agents or their combination was assessed using the mean change in the disease activity score (DAS) and the ACR improvement criteria. RESULTS: Four RCTs were identified to compare the efficacy of the combination MTX-SSZ to the efficacy of either drug alone. Two parallel trials were performed with patients naïve to both drugs and two add-on trials were performed in SSZ failures. In the trials with naïve patients, the mean DAS changes for the combination MTX and SSZ pointed to a sub-additive efficacy. In the trials with patients who previously failed to SSZ, the mean DAS changes for the combination MTX and SSZ indicated additive efficacy. CONCLUSIONS: In RA, addition of MTX to SSZ is a therapeutic option in SSZ failures, whereas combination of MTX and SSZ in DMARD-naïve patients has no added value.

Methotrexate therapy in rheumatoid arthritis after failure to sulphasalazine: to switch or to add?

OBJECTIVES: MTX, either alone or in combination with SSZ, is effective in the treatment of RA. Trials have shown that, after SSZ failure, the addition of MTX to SSZ is more effective than a switch to MTX. Whether this is also the case in daily practice has not been analysed yet. In this study, we compared the efficacy of a switch to MTX monotherapy with that of the addition of MTX to SSZ in the daily clinical practice of RA patients who had failed SSZ monotherapy in the Nijmegen RA Inception Cohort. METHODS: For this study, 230 patients who failed to SSZ monotherapy were followed for up to 52 weeks. A total of 124 underwent a switch to MTX alone, whereas 106 patients received the combination of MTX and SSZ. The primary outcome measure was the mean change in the disease activity score (DAS28) after 24 weeks. RESULTS: Both treatment groups showed a significant decrease in DAS28 after 24 weeks, which was similar in both groups. Drug survival analysis showed that the chance to stop with a DMARD within 52 weeks was higher in the MTX-SSZ group (P <0.01). CONCLUSIONS: In RA patients who failed to SSZ the clinical efficacy of a switch to MTX monotherapy was similar to that of the addition of MTX, suggesting that in daily clinical practice a switch to MTX is a good option for patients with an inadequate response to SSZ.

Treatment of osteoporosis in renal insufficiency.

Patients with osteoporosis often have chronic kidney disease (CKD). CKD is associated with bone and mineral disturbances, renal osteodystrophy, which like osteoporosis leads to a higher risk of fractures. Bisphosphonates are first-line therapy for osteoporosis; however, these are contra-indicated in patients with a GFR <30 ml/min. In this article, we have reviewed the diagnosis and treatment of osteoporosis in moderate to severe renal failure from data of clinical trials. Results have shown that osteoporosis patients and severe CKD with no signs of renal osteodystrophy, oral bisphosphonates (risedronate) seem to be a safe choice. Renal function and PTH should subsequently be monitored strictly. Denosumab, with regularly monitoring of calcium and adequate vitamin D levels or raloxifene are a possible second choice. In any case, one should be certain that there is no adynamic bone before treatment can be started. If there is any doubt, bone biopsies should be taken.

Time to achieve remission determines time to be in remission.

INTRODUCTION: Though remission is currently a treatment goal in patients with rheumatoid arthritis (RA), the number of patients who achieve and sustain remission in daily practice is still small. It is suggested that early remission will be associated with sustainability of remission. The aim was to study the association between time-to-remission and sustainability of remission in a cohort of early RA patients treated according to daily practice. METHODS: For this study, three-year follow-up data were used from the Nijmegen RA Inception Cohort of patients included between 1985 and 2005 (N=753). Patients were included upon diagnosis (ACR criteria), were systematically evaluated at three-monthly visits and treated according to daily practice. Remission was defined according to the Disease Activity Score (DAS)<1.6 and the ACR remission criteria. Remission of at least 6 months duration was regarded as sustained remission. Predictors for time-to-remission were identified by Cox-regression analyses. The relation between time-to-remission and sustained remission was analyzed using longitudinal binary regression. RESULTS: N=398 (52%) patients achieved remission with a median time-to-remission of 12 months. Male gender, younger age and low DAS at baseline were predictive to reach remission rapidly. There were n=142 (36%) patients experiencing sustained remission, which was determined by a shorter time-to-remission only. The relationship between time-to-remission and sustained remission was described by a significant odds ratio (1.11) (1.10 to 1.12-95% CI) that was constant over the whole period 1985 to 2005. Results obtained with the ACR remission criteria were similar. CONCLUSIONS: A shorter time-to-remission is related to sustainability of remission, supporting striving for early remission in patients with RA.

[Practice guideline 'Diagnosis and treatment of rheumatoid arthritis']. / Richtlijn 'Diagnostiek en behandeling van reumatoïde artritis'.

Treatment early in the course of the disease, along with early diagnosis, has a positive influence on clinical outcome in patients with rheumatoid arthritis (RA). Therapeutic strategies, including the use of 'disease-modifying antirheumatic drug' (DMARD) combinations, have proved effective, with relatively few side effects. New insights into the pathophysiology of RA have lead to the development of novel therapeutic agents that have been demonstrated to be highly effective. Patients should be monitored intensively with respect to the effect of therapy on reduction of disease activity, followed by modification of therapeutic strategy in the case of a suboptimal treatment response. Various non-pharmacological interventions, such as exercise therapy and patient education, are available to help patients to cope with the consequences of the disease. Optimizing treatment of RA by means of this approach will help to realize the goal of current therapy: to achieve and sustain remission and, thereby, an optimal functional level.