Can we prevent rapid radiological progression in patients with early rheumatoid arthritis?

The aim of this study is to test the performance of a matrix model to predict rapid radiological progression (RRP) in a study population of early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) patients. A matrix model using baseline CRP, erosion score, autoantibody status, and initial treatment choice to predict RRP (increase ≥5 points in Sharp-van der Heijde score (SHS) in 1 year) was derived from the BeSt study where patients with active RA (1987-criteria) were treated with initial monotherapy or combination therapy, aiming at low disease activity. In the IMPROVED study, patients with early RA (2010 criteria) and UA were initially treated with methotrexate and prednisone aiming at remission. A receiver operating characteristics (ROC) curve was used to assess the discriminative value of the model to predict damage progression in the IMPROVED population. Four hundred thirty-one out of 479 patients with RA and 106/122 with UA could be categorized as high, intermediate, low, or very low risk for RRP. One patient, with a very low risk profile, showed RRP. Thirty-two other patients (5 %) showed radiological progression ≥0.5 point SHS; none had a high risk profile and 22 had a very low risk profile. The area under the curve (AUC) of the ROC curve was 0.56 (95% CI 0.45; 0.68). A matrix model predicting RRP based on risk factors identified in recent onset active RA according to the 1987-criteria performed poorly in recent onset RA (2010 criteria) and UA. It appears that known risk factors for damage progression lose their impact with early remission steered treatment, so that RRP might be considered a phenomenon of the past.

Four-month metacarpal bone mineral density loss predicts radiological joint damage progression after 1†year in patients with early rheumatoid arthritis: exploratory analyses from the IMPROVED study.

AIM: To assess whether in early (rheumatoid) arthritis (RA) patients, metacarpal bone mineral density (BMD) loss after 4 months predicts radiological progression after 1 year of antirheumatic treatment. METHODS: Metacarpal BMD was measured 4 monthly during the first year by digital X-ray radiogrammetry (DXR-BMD) in patients participating in the IMPROVED study, a clinical trial in 610 patients with recent onset RA (2010 criteria) or undifferentiated arthritis, treated according to a remission (disease activity score<1.6) steered strategy. With Sharp/van der Heijde progression ≥0.5 points after 1 year (yes/no) as dependent variable, univariate and multivariate logistic regression analyses were performed. RESULTS: Of 428 patients with DXR-BMD results and progression scores available, 28 (7%) had radiological progression after 1 year. Independent predictors for radiological progression were presence of baseline erosions (OR (95% CI) 6.5 (1.7 to 25)) and early DXR-BMD loss (OR (95% CI) 1.5 (1.1 to 2.0)). In 366 (86%) patients without baseline erosions, early DXR-BMD loss was the only independent predictor of progression (OR (95% CI) 2.0 (1.4 to 2.9)). CONCLUSIONS: In early RA patients, metacarpal BMD loss after 4 months of treatment is an independent predictor of radiological progression after 1 year. In patients without baseline erosions, early metacarpal BMD loss is the main predictor of radiological progression.

A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study.

OBJECTIVES: To assess which treatment strategy is most effective in inducing remission in early (rheumatoid) arthritis. METHODS: 610 patients with early rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) started treatment with methotrexate (MTX) and a tapered high dose of prednisone. Patients in early remission (Disease Activity Score <1.6 after 4 months) tapered prednisone to zero and those with persistent remission after 8 months, tapered and stopped MTX. Patients not in early remission were randomised to receive either MTX plus hydroxychloroquine plus sulfasalazine plus low-dose prednisone (arm 1) or to MTX plus adalimumab (ADA) (arm 2). If remission was present after 8 months both arms tapered to MTX monotherapy; if not, arm 1 changed to MTX plus ADA and arm 2 increased the dose of ADA. Remission rates and functional and radiological outcomes were compared between arms and between patients with RA and those with UA. RESULTS: 375/610 (61%) patients achieved early remission. After 1 year 68% of those were in remission and 32% in drug-free remission. Of the randomised patients, 25% in arm 1 and 41% in arm 2 achieved remission at year 1 (p<0.01). Outcomes were comparable between patients with RA and those with UA. CONCLUSIONS: Initial MTX and prednisone resulted in early remission in 61% of patients with early (rheumatoid) arthritis. Of those, 68% were in remission and 32% were in drug-free remission after 1 year. In patients not in early remission, earlier introduction of ADA resulted in more remission at year 1 than first treating with disease-modifying antirheumatic drug combination therapy plus prednisone.

The relationship between disease activity and depressive symptoms severity and optimism--results from the IMPROVED study.

To assess depressive symptoms severity and dispositional optimism in patients with recent onset arthritis both before and after 4 months treatment. Two hundred twenty-two patients with recent onset RA and undifferentiated arthritis in the IMPROVED study filled out the Beck Depression Inventory (BDI-II) to assess depressive symptoms severity and the Life Orientation Test Revised (LOT-R) to measure optimism before and after 4 months of treatment. All patients were treated with methotrexate 25 mg/week and prednisone 60 mg/day (tapered to 7.5 mg/day in 7 weeks). Linear regression analysis was used to assess the association between the disease activity score (DAS) and its components (tender joint count, general well-being measured with a visual analogue scale (VAS), swollen joint count, and erythrocyte sedimentation rate) with the BDI-II an LOT-R scores. In general, depressive symptoms were mild. The DAS was an independent predictor of depressive symptoms scores both at baseline and after 4 months follow-up, in particular tender joint count and VAS global health. Disease activity was not associated with the level of optimism. Nevertheless, patients who achieved clinical remission improved significantly more in both depression score and optimism score than patients who did not. Patients with early arthritis report improvement in depressive symptoms and optimism with improvement in disease activity and achieving clinical remission. Depression scores are associated with pain and unwell being but not with swollen joint counts and inflammatory parameters.

Drug therapy in undifferentiated arthritis: a systematic literature review.

Undifferentiated arthritis (UA) is defined as an inflammatory oligoarthritis or polyarthritis in which no definitive diagnosis can be made. We performed a literature review to assess the efficacy of various drug therapies in patients with UA. The literature search was conducted using electronic databases Pubmed, EMBASE and MEDLINE in adults with UA or early arthritis (not fulfilling the American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism (EULAR) 2010 criteria for rheumatoid arthritis). Drug therapy consisted of disease modifying antirheumatic drugs (DMARDs), biological agents and oral, intramuscular or intra-articular corticosteroids. Nine publications on eight randomised controlled trials (RCTs), two publications on two uncontrolled open-label trials and seven publications on three cohort studies were included. Temporary treatment with methotrexate (MTX), abatacept and intramuscular corticosteroids were demonstrated in RCTs with 12 months to 5 years follow-up to be more effective than placebo in suppressing disease activity or radiological progression. One study suggests that DMARD combination therapy is, at least after 4 months, superior to MTX monotherapy in patients with UA at high risk of developing persistent arthritis. The open-label uncontrolled trials and cohort studies also suggested that early treatment may provide immediate suppression of inflammation. The long-term benefit of early treatment in UA remains unclear. In conclusion, patients with UA benefit from early treatment with MTX. Combining multiple DMARDs or DMARDs with corticosteroids and biological agents may be even more beneficial. However, which treatment may provide the best results or may alter the disease course has still to be determined. More RCTs with longer follow-up time are needed.

Association of high body mass index with decreased treatment response to combination therapy in recent-onset rheumatoid arthritis patients.

OBJECTIVE: To assess the association between high body mass index (BMI) and treatment response in recent-onset rheumatoid arthritis. METHODS: In the Behandelstrategieën voor Reumatoide Artritis (Treatment Strategies for Rheumatoid Arthritis) study, 508 patients were randomized to initial monotherapy or combination therapy with prednisone or infliximab (IFX). The response to Disease Activity Score (DAS) ≤2.4-steered treatment (first dose and after 1 year) was compared between patients with a BMI <25 kg/m(2) and ≥25 kg/m(2) , using relative risk (RR) regression analyses. DAS, components of DAS, and functional ability during the first year were compared using linear mixed models. RESULTS: High BMI was independently associated with failure to achieve a DAS ≤2.4 on initial therapy (RR 1.20 [95% confidence interval (95% CI) 1.05, 1.37]). The effect for combination therapy with prednisone was RR 1.55 (95% CI 1.06, 2.28) and for combination therapy with IFX 1.42 (95% CI 0.98, 2.06). The RRs for failure after 1 year were 1.46 (95% CI 0.75, 2.83) and 2.20 (95% CI 0.99, 4.92), respectively. High BMI was also associated with failure on delayed combination therapy with IFX, after adjustment for selection bias related to previous failure on disease-modifying antirheumatic drugs. No significant association was observed in the initial monotherapy groups. In the first year, patients with a high BMI had higher DAS and worse functional ability, with more tender joints and a higher visual analog scale global health, but not more swollen joints and similar systemic inflammation. CONCLUSION: High BMI was independently associated with failure to achieve low DAS on initial combination therapy with prednisone and on initial and delayed treatment with IFX. Patients with a high BMI experienced more pain, but not more swelling or systemic inflammation.

Are claims of advertisements in medical journals supported by RCTs?

BACKGROUND: Claims made in advertisements in medical journals might not always be supported by high-quality evidence, and referenced studies may have been sponsored by the pharmaceutical industry itself. We studied to what extent randomised controlled trials (RCTs) support the claims in advertisements in leading medical journals. METHODS: Consecutive unique advertisements were selected from nine different medical journals, and evaluated by 250 medical students using a standardised score form. The quality of RCTs that were referenced in these advertisements was assessed with an instrument based on the Chalmers' score. RESULTS: 158 RCTs from 94 advertisements were used in the study. In total 55% of the RCTs had a high-quality score, 44% intermediate, and <1% had a low-quality score. Almost 40% of the RCTs had a high-quality score and at the same time supported the claim for which they were cited, while only 17% were also not sponsored by a pharmaceutical company. CONCLUSION: RCTs used to support claims in medical advertisements are often not a high-quality and independent source of evidence. This distracts from the credibility of claims in advertisements, even in the high-ranked journals.