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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

Introduction Myasthenia gravis is an autoimmune disease affecting the neuromuscular junction, often associated with other autoimmune diseases, including rheumatoid arthritis. Patients with rheumatoid arthritis present an increased prevalence of myasthenia gravis compared to the general population. While these two diseases share some therapeutic options, such as glucocorticoids, methotrexate, and rituximab, there are no guidelines for treating concomitant disease. We aim to review the available evidence and to discuss the efficacy and safety of the therapeutic options in patients with rheumatoid arthritis associated with myasthenia gravis. Method We described three patients with rheumatoid arthritis associated with myasthenia gravis and we performed a systematic review of the associated literature. Results A 48-year-old man and two women (48 and 55 years old) with concomitant diagnoses of active rheumatoid arthritis and well-controlled myasthenia gravis are described. They were treated with methotrexate, leflunomide, upadacitinib, and adalimumab. None of them experienced changes in their myasthenic symptoms. We found 9 additional cases from our literature review. Methotrexate, rituximab, upadacitinib, diphenyl sulfone, auranofin, and loxoprofen sodium did not show an impact on the seven patients with previously well-controlled myasthenia. Glucocorticoids, methotrexate, and rituximab proved effective in active myasthenia gravis and arthritis. Conflicting data emerged for Tumor-necrosis factor inhibitors. Conclusions Although the available evidence remains scarce, we consider glucocorticoids, methotrexate, and rituximab as safe and effective options. The role of tumor-necrosis factor inhibitors remains uncertain. Eventually, Janus Kinase inhibitors are a novel interesting option for these patients. Key Points• To date, the only evidence on the treatment of patients with rheumatoid arthritis and concomitant myasthenia gravis derives from case reports.• Based on the review of the available case reports and on the cases we described, we consider glucocorticoids, methotrexate, and rituximab as safe and effective options, while the role of Tumor-necrosis factor inhibitors remains uncertain.• Based on the cases we described, Janus Kinase inhibitors are a novel interesting option for patients with concomitant rheumatoid arthritis and myasthenia gravis.

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.