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IntroductionGlucocorticoids are still a mainstream of rheumatoid arthritis (RA) treatment. Reducing glucocorticoids should be attempted in all patients. However, choosing the right tapering strategy is challenging. The primary aim of our study is to determine the dose–response association between glucocorticoid tapering and risk of flare in RA.MethodsWe conducted a case-crossover study to determine the factors associated to higher risk of flare in patients with RA. In case-crossover studies time-varying factors are assessed before events (hazard periods) and before control periods. We defined hazard periods as the 6 months immediately preceding flares of RA. Control periods were the 6 months prior to visits without flare. Exposure of interest was the tapering of glucocorticoids to various doses.Results508 patients with RA were included in the study and 267 (52.5%) had at least a flare and served as the case-crossover study population. 1545 visits were available for analysis and 345 (22.3%) flares were recorded. Discontinuation of glucocorticoids (ie, tapering to doses of 0 mg/day) and tapering to 0–2.5 mg/day was associated with higher risk of flare (adjusted OR (aOR) of 1.45, 95% CI: 1.13 to 2.24 and aOR of 1.37; 95% CI: 1.06 to 2.01, respectively). Tapering to doses >2.5 mg/day was not associated with significantly higher risk of flare.ConclusionsWe found that tapering to doses of >2.5 mg/day was generally effective in terms of risk of flare. Flare risk was higher when glucocorticoids were tapered to doses ≤2.5 mg/day. Our study might help design new tapering strategies in patients with RA on biological disease-modifying antirheumatic drugs.

ObjectiveThe negative effects of glucocorticoids on bone depend on dose and treatment duration. However, it is unclear whether a safe dose exists, especially for patients with inflammatory rheumatic musculoskeletal diseases (iRMDs). We undertook this study to determine the effects of glucocorticoid doses on bone health in iRMD patients.MethodsWe conducted a longitudinal cohort study on women with iRMD. Bone mineral density (BMD) and fractures were assessed prospectively and compared to a matched cohort without iRMD. Kaplan‐Meier curves with log rank test were made for iRMD patients (stratified for glucocorticoid use and dose) and the matched cohort. Multivariable Cox regression survival models were also employed to analyze the effect of glucocorticoids on fracture.ResultsA total of 884 women with iRMD and 1,766 controls (matched for age, T score, and 10‐year fracture risk) were included in the study and followed up for up to 6 years. BMD decreased significantly in all patients receiving glucocorticoids who were not receiving anti‐osteoporosis treatment (–4.26% for ≥5 mg/day of prednisone equivalent, P = 0.0011; –4.23% for 2.5–5 mg/day, P = 0.0422; –2.66% for 0–2.5 mg/day, P = 0.0006). Anti‐osteoporosis treatment (largely bisphosphonates) prevented bone loss only in patients receiving <5 mg/day of prednisone equivalent. Fracture incidence was higher in patients with iRMD compared to controls, but only glucocorticoid doses ≥5 mg/day were associated with significantly higher risk of fracture.ConclusionGlucocorticoid doses as low as 2.5 mg/day were associated with BMD loss in iRMD patients, but this effect was preventable. BMD loss in patients receiving ≥5 mg/day was not totally prevented by anti‐osteoporosis medications currently used in clinical practice, resulting in higher risk of fracture.image

BackgroundSarcopenia is a progressive and generalized skeletal muscle loss associated with falls, fractures, physical disability, and mortality, described as age-related or secondary. Systemic inflammatory diseases, such as rheumatoid arthritis (RA), are well-known causes of secondary sarcopenia. However, the exact prevalence of sarcopenia in patients with RA is still unknown, partly due to the heterogeneous definitions of sarcopenia adopted in different studies.ObjectivesTo assess the prevalence of sarcopenia in a cohort of patients affected by RA, and to evaluate the influence of age, sex, comorbidity, disease duration and activity, antibody status and therapies on sarcopenia.MethodsWe conducted a retrospective observational study on adult patients affected by RA undergoing evaluation at our outpatient clinic from January 2009 and July 2021. All patients underwent dual-energy X-ray absorptiometry (DXA) for assessment of body composition; diagnosis of sarcopenia was defined using Skeletal Muscle Mass Index (SMI), as proposed by consensus EWGSOP2 (1). We collected relevant demographic, clinical, therapeutic, and laboratory data at the time of DXA. We excluded patients affected by neoplastic disorders and/or malnutrition. Binary logistic regression analysis was employed to define predictors and protective factors of developing sarcopenia.ResultsA total of 266 patients (82.7% women) with a median age of 58.4 (IQR 14.4) years were included in the study. The prevalence of sarcopenia was 27.44%. From the binary logistic regression analysis, we found that the use of oral glucocorticoids (GCs) at a daily dose > 3.25 mg of prednisone-equivalent was significantly associated with sarcopenia (β 0.68, p = 0.047, aOR 1.98, 95% CI 1.009 – 3.881) (Figure 1). We found a significant inverse correlation between conventional disease-modifying antirheumatic drug (c-DMARDs) and sarcopenia (β -0.71, p = 0.027) as well. Age, sex, disease duration, mean disease activity - expressed as disease activity score based on 28 joints (DAS-28), erosive and seropositive disease - and biologic disease-modifying antirheumatic drug (b-DMARDs) therapy were not predictors of sarcopenia, albeit seropositive status showed a correlation trend with increased prevalence of sarcopenia (p = 0.092).Figure 1.ConclusionOur study showed that sarcopenia is a common complication in RA. Glucocorticoid therapy was associated with an increased prevalence of sarcopenia, while c-DMARDs acted as protective factors, possibly decreasing chronic inflammation. No correlation was found with b-DMARDs, possibly due to association with longer and more aggressive rheumatic disease.References[1]Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:16–31Disclosure of InterestsNone declared

The effects of different cholecalciferol supplementation regimens on serum inflammatory cytokines in healthy subjects with vitamin D deficiency are still lacking. This is a single-center, open-label, randomized, parallel group study involving healthy subjects deficient in vitamin D (baseline 25OHD < 20 ng/mL) receiving oral cholecalciferol with three different dosing regimens: Group A: 10,000 IU/day for 8 weeks followed by 1000 IU/day for 4 weeks; Group B: 50,000 IU/week for 12 weeks and Group C: 100,000 IU every other week for 12 weeks. IL-17A, IL-6, IL-8, IL-10, IL-23 and TNFα were measured at baseline and at week 4, 8, 12, and 16. 75 healthy subjects were enrolled (58.7% female), with an average age of 34.1 ± 10.2 years. No statistical differences were observed among groups at baseline for either IL-6, IL-17A, IL-23, IL-8 or IL-10 at any time point; TNFα was indetectable. Concerning the whole sample, the time trend analysis showed a statistically significant linear trend for decreasing values over the treatment period for IL-6 (p = 0.016) and IL-17A (p = 0.006), while no significant time trends were observed for the other teste cytokines. No significant differences were found in the serum concentrations of the tested cytokines between week 12 and week 16. In young healthy individuals deficient in vitamin D, cholecalciferol administration showed a decrease in the serum IL-6 and IL-17A concentrations, without marked differences using the three regimens.