Is glucocorticoid bridging therapy associated with later use of glucocorticoids and biological DMARDs during the disease course of patients with rheumatoid arthritis in daily practice? A real-world data analysis.

OBJECTIVE: To evaluate if initially starting glucocorticoid (GC) bridging leads to a higher probability of long-term GC and biological (b)DMARD use in rheumatoid arthritis (RA)-patients. METHODS: Electronical health records data from newly diagnosed RA-patients from the Leiden University Medical Center were used. Patients who started GC as part of initial treatment (iGC group) and who did not (niGC group) were compared in terms of GC and bDMARD use later in the disease course. Multivariable adjustment was performed to account for confounding by indication. RESULTS: 465/932 newly diagnosed RA-patients (50 %) were treated with GC as initial treatment step. Patients in the iGC group were older, included fewer females, had a higher disease activity at baseline compared to the niGC group plus a more rapid decrease in DAS28 in the first 6 months. During follow-up, 42 % of the iGC group started a second course of GC and 17 % started a bDMARD, compared to 34 % and 13 % In the niGC group. The hazard to start a bDMARD later in the disease course was not significantly different between the two groups in two time periods (0.34 95 %CI(0.09;1.21) resp. 1.48 95 %CI (0.98;2.22)), but the hazard to (re)start GC later on was higher for the iGC group (aHR 1.37 95 %CI(1.09;1.73)). CONCLUSION: In this daily practice cohort of newly diagnosed RA patients, patients in the iGC group had a more rapid DAS28 decrease and an increased probability of starting GC later on compared to the niGC group. The probability of bDMARD use was not significantly increased.

No radiographic wrist damage after treatment to target in recent-onset juvenile idiopathic arthritis.

BACKGROUND: To evaluate radiographic progression of patients with new-onset juvenile idiopathic arthritis (JIA) in response to an early, tightly-controlled, treatment-to-target. METHODS: Patients with JIA participating in the BeSt-for-Kids-study, randomized to 3 treatment strategy arms, were eligible if at least 1 conventional wrist-radiograph was available. Bone damage as reflected by carpal length was assessed using the Poznanski-score. The BoneXpert-method was used to determine the Bone Age (BA, > 5 years) and bone mineral density (BMD) of the wrist. These scores were evaluated over time and compared between the treatment arms and mean JADAS10-score using linear mixed models corrected for age and symptom duration. RESULTS: In 60 patients, 252 radiographs were analysed. Baseline age and symptom duration were different between the arms. No difference in comparison to the healthy reference population was found at baseline for the Poznanski-score (IQR varying from - 0,82; 0.68), nor for BA (varying from - 0.88 to 0.74). Baseline BMD was statistically significantly lower in arm 3 (initial treatment with etanercept and methotrexate) (- 1.48; - 0.68) compared to arm 1 (- 0.84; - 0.04) and arm 2 (- 0.93; 0.15). After treatment to target inactive disease, the Poznanski-scores and the BA remained clinically unchanged, while the BMD in arm 3 improved (p < 0.05 vs arm 1). CONCLUSIONS: Recent-onset JIA patients, treated-to-target aimed at inactive disease, showed no signs of radiographic wrist damage (Poznanski-score, BA or BMD) either at baseline or at follow-up, irrespective of treatment arm. A lower BMD at baseline in arm 3, initially treated with methotrexate and etanercept, improved significantly after treatment. TRIAL REGISTRATION: NTR, NL1504 (NTR1574). Registered 01-06-2009.

Is current smoking status and its relationship to anti-cyclic citrullinated peptide antibodies a predictor of worse response to biological therapies in rheumatoid arthritis patients?

OBJECTIVE: To assess the association between smoking, anti-cyclic citrullinated peptide (anti-CCP) antibody status, and clinical efficacy of biological therapies in rheumatoid arthritis (RA) patients. METHOD: This retrospective clinical practice setting study included 1349 RA patients from the METEOR database (aged >18 years). We collected data on sociodemographics, smoking status (smoker, <10, 10-19, and >20 cigarettes/day; ex-smoker; non-smoker), baseline disease activity parameters and anti-CCP, previous disease-modifying anti-rheumatic drugs (DMARDs), biological therapy, combined therapy (steroids and DMARDs), and follow-up disease activity. Clinical efficacy was assessed by European League Against Rheumatism (EULAR) good/moderate response rates for all aggregated biological therapies, based on both smoking and anti-CCP status. RESULTS: The non-smoking RA patients were more often female at biological therapy initiation than the ex-smokers and smokers (91.1% vs 60.4% and 67.9%, respectively, p < 0.001), and ex-smokers were older than non-smokers and smokers (mean ± sd 56.5 ± 11.1, 53.5 ± 13.3 and 51.3 ± 11.0 years old, respectively; p < 0.001). In total, 845 (62.6%) were non-smokers, 214 (15.9%) ex-smokers, and 290 (21.5%) smokers [daily cigarettes smoked: 148 (11%) <11; 61 (4.5%) 11-20; and 81 (6%) >20]. Anti CCP-antibody status was similar in both groups. Non-smokers showed higher baseline DAS28 than ex-smokers and smokers (5.0 ± 1.5 vs 4.7 ± 1.4 and 4.7 ± 1.4, respectively; p < 0.001) and used more baseline steroids and DMARDs. A higher EULAR response rate was observed in non-smokers than in ex-smokers and smokers (73% vs 65% and 64.1%, respectively; p = 0.004). Drug survival was higher in non-smokers compared to ex-smokers and smokers [57.7 months (46.4-53.8), 38.6 (30.3-46.8), and 50.1 (41.8-58.4); p < 0.001, respectively]. CONCLUSION: In daily clinical practice, non-smokers respond better than smokers to biological therapy, but this does not result in better drug survival.

Meta-Regression of a Dose-Response Relationship of Methotrexate in Mono- and Combination Therapy in Disease-Modifying Antirheumatic Drug-Naive Early Rheumatoid Arthritis Patients.

OBJECTIVE: To investigate a possible short-term dose-response relationship of initial treatment with methotrexate (MTX) in monotherapy and combination therapy in recent-onset rheumatoid arthritis (RA) patients. METHODS: A systematic literature search was performed on trials and cohorts, including early, disease-modifying antirheumatic drug (DMARD)-naive RA patients treated with MTX, with data on clinical results within 6 months from treatment start. Cohen's effect sizes were calculated for the Health Assessment Questionnaire (HAQ), erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) level, and/or Disease Activity Score (DAS)/in 28 joints (DAS28) in 4 treatment groups: MTX monotherapy, or MTX in combination with synthetic (cs) DMARDs, biologic (b) DMARDs, or glucocorticoids. Random-effects meta-regression analyses were performed for each outcome, with treatment group as the predictor corrected for baseline HAQ or disease activity and assessment point. RESULTS: Thirty-one studies including 5,589 patients were included. The meta-regression did not support higher effectiveness of increasing MTX dose in monotherapy. The number of treatment groups using combination therapy with csDMARDs was too small to perform meta-regression analyses. In combination therapy with glucocorticoids, a higher MTX dose was associated with higher (worse) outcome HAQ, but not with DAS/DAS28 or ESR/CRP level. In combination therapy with bDMARDs, a higher MTX dose was associated with higher outcome HAQ and DAS/DAS28, but not with ESR/CRP level. All effect sizes were small. CONCLUSION: In DMARD-naive, early RA patients who start MTX, either as monotherapy or in combination with bDMARDs or glucocorticoids, a higher initial dose of MTX was not associated with better clinical outcomes. This finding suggests that there is little short-term gain from starting with high compared to low MTX doses.

Running with a minimalist shoe increases plantar pressure in the forefoot region of healthy female runners.

OBJECTIVES: Minimalist running shoes have been proposed as an alternative to barefoot running. However, several studies have reported cases of forefoot stress fractures after switching from standard to minimalist shoes. Therefore, the aim of the current study was to investigate the differences in plantar pressure in the forefoot region between running with a minimalist shoe and running with a standard shoe in healthy female runners during overground running. DESIGN: Randomized crossover design. METHODS: In-shoe plantar pressure measurements were recorded from eighteen healthy female runners. Peak pressure, maximum mean pressure, pressure time integral and instant of peak pressure were assessed for seven foot areas. Force time integral, stride time, stance time, swing time, shoe comfort and landing type were assessed for both shoe types. A linear mixed model was used to analyze the data. RESULTS: Peak pressure and maximum mean pressure were higher in the medial forefoot (respectively 13.5% and 7.46%), central forefoot (respectively 37.5% and 29.2%) and lateral forefoot (respectively 37.9% and 20.4%) for the minimalist shoe condition. Stance time was reduced with 3.81%. No relevant differences in shoe comfort or landing strategy were found. CONCLUSIONS: Running with a minimalist shoe increased plantar pressure without a change in landing pattern. This increased pressure in the forefoot region might play a role in the occurrence of metatarsal stress fractures in runners who switched to minimalist shoes and warrants a cautious approach to transitioning to minimalist shoe use.

A systematic review into the effectiveness of hand exercise therapy in the treatment of rheumatoid arthritis.

Hand exercises are often part of the treatment of hand rheumatoid arthritis; however, it is still unclear whether and what type of exercises is effective in the treatment of this condition. Therefore, a systematic review into the effectiveness of hand exercises in the treatment of hand rheumatoid arthritis has been performed. Studies were identified in the literature databases by predefined search criteria. The eight included studies are peer-reviewed studies published between 2000 and 2014. Hand exercises differed between studies, but always included resistance and/or active range of motion exercises. Grip strength in various grip types (power grip, key pinch, precision pinch and tripod pinch) was found to improve by hand exercise therapy without having adverse effects on pain or disease activity. Adaptations in the range of motion in response to hand exercise therapy were less pronounced. There appears to be some transfer from the improvements on the body functioning level to the level of daily functioning, with the largest improvements found on grip ability. With regard to the intervention content, there was some evidence in favour of a longer therapy duration and a higher therapy intensity. No conclusions could be drawn on the effectiveness of the different types of exercises. Collectively, the studies indicate that hand exercises may have positive effects on strength and some aspects of daily functioning without aggravating disease activity or pain, although caution should be taken for subjects in the exacerbation period.