Long-Term Bone Mineral Density Changes in Kidney Transplant Recipients Treated with Denosumab: A Retrospective Study with Nonequivalent Control Group.

Data on the effectiveness of denosumab on osteoporosis after kidney transplantation are limited. We investigated the long-term bone mineral density (BMD) changes in kidney transplant recipients (KTRs) treated with denosumab compared to untreated KTRs. We enrolled KTRs treated with denosumab 60 mg/6 months for 4 years. An untreated group of sex and age-matched KTRs with a 1:1 ratio was included. The primary outcome was BMD changes assessed by Dual-energy X-ray Absorptiometry over 4 years. Data on serum creatinine, alkaline phosphatase (ALP), parathyroid hormone, and 25-hydroxyvitamin D were collected. All patients received oral cholecalciferol and calcium supplementation. 23 denosumab-treated KTRs were enrolled, and 23 untreated KTRs. The median time from transplant to the start of denosumab was 4 years (range 0:24). The denosumab group showed a significant increase from baseline in BMD at the lumbar spine (LS) (9.0 ± 10.7%, p < 0.001), and total hip (TH) (3.8 ± 7.9%, p = 0.041). The untreated group showed a significant decrease at all sites (- 3.0 ± 7%, p = 0.041 at the LS; - 6.3 ± 9.2%, p = 0.003 at the TH; - 6.7 ± 9.3%, p = 0.003 at the FN). The between-group differences in percent BMD changes were statistically significant at all sites. Similar results were found for the respective Z-scores. The ALP serum levels significantly decreased from baseline only in the denosumab group, with a significant between-group difference (p = 0.032). No significant differences in serum creatinine, hypocalcaemic events or acute graft rejection rates were observed. Four years of denosumab therapy were associated with increased BMD in KTRs, while untreated KTRs showed significant BMD losses at all sites.

Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Depression as a possible determinant of fatigue in patients with axial spondyloarthritis.

OBJECTIVES: Fatigue is a common comorbidity in patients with axial spondyloarthritis (axSpA), often reported also by those in clinical remission or with moderate disease activity. The aim of this study is to assess the prevalence of fatigue in patients with axSPA, and to investigate possible non-disease-related determinants, with a special focus on depression. METHODS: Patients with axSpA were assessed using the Chalder's Fatigue Questionnaire (CFQ) for fatigue, and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) for depression. Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI) and Health Assessment Questionnaire (HAQ) were also used to assess disease activities and disability. Univariate and multivariate linear regressions were performed to identify possible predictors of fatigue. RESULTS: Out of 119 patients, 53 (44.5%) had fatigue. Patients with fatigue had higher HADS-D, ASDAS, BASFI, HAQ scores. HADS-D was predictive of CFQ score in univariate and multivariate regressions for total CFQ, and for mental and physical subscales. The correlation between HADS-D and CFQ total score was statistically significant also when taking into consideration only patients in clinical remission and with moderate disease activity. Depressed patients had higher CFQ score compared to non-depressed ones, and did not show any difference in CFQ scores when stratified for disease activity or systemic inflammation. CONCLUSIONS: The study found correlation between fatigue and disease activity and depression in patients with axSpA. These findings suggest that depression could represent the major determinant of fatigue in patients with axSpA, independently of clinical activity.

The potential pathogenic role of gut microbiota in rheumatic diseases: a human-centred narrative review.

A growing amount of evidence suggests that gut microbiota plays an important role in human health, including a possible role in the pathogenesis of rheumatic and musculoskeletal diseases (RMD). We analysed the current evidence about the role of microbiota in rheumatoid arthritis (RA), spondyloarthritis (SpA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). In RA, we found a general consensus regarding a reduction of diversity and a specific bacterial signature, with consistent changes according to the different ethnic and geographical areas. The major pathogenetic role in RA is recognised for P. copri, L. salivarius and Collinsella, even if findings become more heterogeneous when considering established disease. In SpA, we found a relative gut abundance of Akkermansia, Coprococcus, Ruminoccocus and a relative reduction in Bacterioides and Firmicutes spp. Human and preclinical data suggest loss of mucosal barrier, increased permeability and Th1- and Th17-mediated inflammation. Additionally, HLA-B27 seems to play a role in shaping the intestinal microbiota and the consequent inflammation. In SLE, the typical gut microbiota signature was characterised by a reduction in the Firmicutes/Bacteroidetes ratio and by enrichment of Rhodococcus, Eggerthella, Klebsiella, Prevotella, Eubacterium and Flavonifractor, even if their real pathogenic impact remains unclear. In SSc, gastrointestinal dysbiosis is well documented with an increase of pro-inflammatory species (Fusobacterium, Prevotella, Ruminococcus, Akkermansia, γ-Proteobacteria, Erwinia, Trabsulsiella, Bifidobacterium, Lactobacillus, Firmicutes and Actinobacteria) and a reduction of species as Faecalibacterium, Clostridium, Bacteroidetes and Rikenella. In conclusion, seems possible to recognise a distinct gut microbiota profile for each RMD, even if significant differences in bacterial species do exist between different studies and there is a high risk of bias due to the cross-sectional nature of such studies. Therefore longitudinal studies are needed, especially on patients with preclinical and early disease, to investigate the real role of gut microbiota in the pathogenesis of RMD.

Machine learning to characterize bone biomarkers profile in rheumatoid arthritis.

Background: Bone metabolism is disrupted in rheumatoid arthritis (RA); however, the bone metabolic signature of RA is poorly known. The objective of the study is to further characterize the bone metabolic profile of RA and compare it to psoriatic arthritis (PsA), systemic sclerosis (SSc) and healthy controls. Methods: We did a cross-sectional case-control study on consecutively enrolled patients and age-matched controls. We collected clinical characteristics, serum biomarkers related to bone metabolism and Bone Mineral Density (BMD). A multiple correlation analysis using Spearman's rank correlation coefficient was conducted within the RA patient group to investigate associations between biomarker levels and clinical variables. Machine learning (ML) models and Principal Component Analysis (PCA) was performed to evaluate the ability of bone biomarker profiles to differentiate RA patients from controls. Results: We found significantly lower BMD in RA patients compared to PsA, and Systemic Sclerosis SSc groups. RA patients exhibited higher Dkk1, sclerostin and lower P1nP and B-ALP levels compared to controls. No significant differences in CTX levels were noted. Correlation analysis revealed associations between bone biomarkers and clinical variables. PCA and ML highlighted distinct biomarker patterns in RA which can effectively discriminated bone biomarkers profile in RA from controls. Conclusion: Our study helped uncover the distinct bone profile in RA, including changes in bone density and unique biomarker patterns. These findings enhance our comprehension of the intricate links between inflammation, bone dynamics, and RA activity, offering potential insights for diagnostic and therapeutic advancements in managing bone involvement in this challenging condition.

Changes in bone turnover markers and bone modulators during abatacept treatment.

Rheumatoid arthritis (RA) causes bone loss, only partly related to inflammation. The impact of RA treatments on bone metabolism and their ability to mitigate bone loss remains uncertain. The primary goal of our study was to examine the influence of abatacept on serum levels of markers and regulators involved in bone turnover. Secondary objectives included evaluating changes in bone mineral density (BMD), bone health parameters, erosions, and exploring potential correlations among these parameters. We conducted a prospective observational study on patients with active seropositive RA failure to biological disease modifying anti-rheumatic drugs initiating treatment with abatacept. We measured at baseline and after 1, 2, 3, 6, 9 and 12 months: serum bone turnover markers (CTX, P1nP, B-ALP), bone modulators (Dkk-1, sclerostin, vitamin D, PTH, OPG and RANKL), BMD and radiographic parameters (modified Sharp van der Heijde score [mSvdH], bone health index [BHI] and metacarpal index [MCI]). Disease activity and glucocorticoid intake was monitored. 33 patients were enrolled in the study. We found a significant increase in markers of bone formation (B-ALP and P1nP) from baseline to M6 and M12. PTH increased significantly at M6 but not at M12. All other bone markers and modulators did not change. We found a significant decrease in BHI and MCI from baseline to M12 (median difference - 0.17 95% CI - 0.42 to - 0.10, p 0.001 and - 0.09 95% CI - 0.23 to - 0.07, respectively). BMD at femoral neck transitorily decreased at M6 (mean difference - 0.019 g/cm2 95% CI - 0.036 to - 0.001 p 0.04). BMD at total hip, lumbar spine and mSvdH score did not change significantly. P1nP delta at M12 correlated with delta mSvdH. Treatment with abatacept was associated with a significant increase in bone formation markers. The secondary and transient increase in PTH serum levels may be responsible of the transitory bone loss.

Comparison and potential determinants of health-related quality of life among rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis: A cross-sectional study.

OBJECTIVES: This study aimed to compare the health-related quality of life scores among rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis and to evaluate socio-demographic and clinical determinantes of quality of life across diseases. METHODS: The sample comprised 490 patients with rheumatoid arthritis, 198 with psoriatic arthritis, and 119 with spondyloarthritis who completed a series of health examinations and self-reported questionnaires. Quality of life was evaluated using the Short-Form 36 Health Survey, disease activity by DAS28-CRP, DAPSA, and ASDAS-CRP (for rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis, respectively), depression and anxiety using the Hospital Anxiety and Depression Scale. ANOVA was used to compare the quality of life dimensions and their physical and mental summary measures among rheumatic diseases, and multivariate analysis was used to explore their potential determinants. RESULTS: Rheumatoid arthritis had significantly worse scores than spondyloarthritis in the following dimensions: physical functioning, role limitation due to physical health, physical component score, and mental health. Psoriatic arthritis was not significantly different from the other two diseases. Multivariate analysis revealed that physical quality of life was mainly associated with disease activity across rheumatic diseases, rheumatological treatment and depression in rheumatoid arthritis and psoriatic arthritis. Mental quality of life is primarily associated with depression and anxiety across rheumatic diseases. CONCLUSION: There were differences in quality of life among patients with inflammatory rheumatic diseases, but overall, approximately uniform factors explained the variance in quality of life across diseases. Clinicians should develop general approaches and strategies for inflammatory rheumatic diseases to improve patients' quality of life.

Ultrasonographic non-radiographic erosions could predict the efficacy of belimumab in articular systemic lupus erythematosus.

The aim of this study is to characterise lupus-related arthritis and assess if the presence of ultrasound-detected erosions could be associated with belimumab in the treatment of systemic lupus erythematosus (SLE) articular manifestations. We performed a spontaneous, monocentric, retrospective, and observational study. We enrolled patients affected by SLE with articular involvement treated with belimumab. We excluded patients with positive rheumatoid factor (RF) or anti-citrullinated peptide antibody (ACPA), Jaccoud's arthropathy, and radiographic erosions. Patients were assessed at baseline, 3, and 6 months. We collected laboratory and clinical data from electronic records. Joint disease activity was assessed using disease activity score on 28 joints based on C-reactive protein (DAS28-CRP), swollen and tender joints count. All patients underwent an ultrasound examination of the wrist, metacarpophalangeal, proximal interphalangeal, and metatarsal-phalangeal joints before the initiation of treatment with belimumab. We performed Student's T-test and Mann-Whitney's U-test to assess the difference between means and Fisher's exact test to assess difference in proportions, and linear univariate regression to investigate predictors of disease activity. We enrolled 23 patients (female 82.6%, mean age of 50.65 ± 14.1 years). Seven patients (30.4%) presented bone erosions at baseline. Patients with bone erosions were generally older (61 ± 16.1 vs 46.13 ± 10.7 years, p = 0.016), more frequently male (42.8 vs 6.2%, p = 0.03), with higher baseline CRP levels (10.29 ± 11.6 vs 2.25 ± 3.1 mg/L, p = 0.015) and C4 levels (0.19 ± 0.17 vs 0.1 ± 0.04 g/L, p = 0.05). After 6 months of treatment with belimumab, patients without erosions improved their DAS28-CRP significantly (2.95 ± 0.89 vs 2.26 ± 0.48, p = 0.01), while patients with erosions did not (3.6 ± 0.79 vs 3.2 ± 0.95, p = 0.413). DAS28-CRP did not differ between the two groups at baseline, while it was significantly lower at the other two time points in patients without erosions. The majority of patients achieved remission at 6 months follow-up based on DAS28-CRP criteria (73.9%), with a significant difference between patients with and without erosions (42.8 vs 87.5%, p = 0.045). The presence of articular ultrasound-detected erosions could be predictive of a decreased efficacy of belimumab in the articular manifestations of SLE. A possible explanation is a rheumatoid-like articular phenotype, despite the lack of ACPA-positivity and radiologic erosions. However, due to the small sample population, larger cohorts are needed to assess the possible predictive role of this finding.

Coping strategies, emotional distress and perceived disease severity in a cohort of patients with rheumatoid arthritis: a mediation analysis.

OBJECTIVES: Few data are available on the role of emotional distress as a possible mediator of the relationship between coping strategies and the Patient Global Assessment (PGA). This study aims to investigate, in a large cohort of patients affected by RA, the relationship between specific copying strategies and PGA, and the role of emotional distress as a mediator. METHODS: A total of 490 patients with RA completed a set of standardized assessments including the self-reported PGA, the Coping Orientation to the Problems Experienced (COPE-NVI) and the Hospital Anxiety and Depression Scale (HADS). A mediation analysis was conducted to investigate the role of emotional distress. RESULTS: The effect of coping strategies on the PGA score was significantly mediated by the emotional distress for religious (total effect mediated 42.0%), planning (total effect mediated 17.5%), behavioural disengagement (total effect mediated 10.5%), and focus on and venting of emotions (total effect mediated 9.8%). Seven coping strategies (acceptance, positive reinterpretation and growth, active coping, denial, humour, substance use-mental disengagement) resulted directly associated to PGA total score, but no mediation effect was found. The remaining four coping strategies were not associated to the PGA score. CONCLUSION: This study suggests that coping strategies could be an important factor in the perceived disease severity. Consequently, in order to reduce PGA in patients with RA, a useful tool could be represented by the implementation of psychological interventions aiming to modify the specific coping styles. Moreover, to prevent or treat emotional distress seems to further reduce PGA.

Clinical and psychological characteristics associated with negative beliefs and concerns about treatment necessity in rheumatic diseases.

Identifying factors that influence problematic beliefs and behaviors related to pharmacotherapy may be useful for clinicians to improve the patients' adherence. The study aims to assess patients' beliefs about the necessity and concerns regarding pharmacotherapy in rheumatic diseases and attitude styles, and to investigate the association between clinical factors and negative beliefs about medication. A sample of 712 patients affected by Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis was enrolled. They were assessed using the Beliefs about Medicines Questionnaires-Specific (BMQ), the Simplified Disease Activity Index (SDAI), the Visual Analogue Scale for pain (VAS), the Chalder Fatigue Scale (CFQ) and the Health Assessment Questionnaire-Disability Index (HAQ-DI). The balance between benefits and costs in the BMQ-Specific was positive in the 79.4% of patients, negative in the 12.1% and equal in the 8.6%. SDAI, taking more than 5 medications, taking anti interleukin 6 (Anti-IL6) or biological disease-modifying antirheumatic drugs (bDMARDs), or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), pain, and fatigue were significantly associated to higher Concerns. Having a longer disease duration was significantly associated with a higher Necessity, together with the current pharmacological treatments and the disability. The multivariate regression models estimated that higher pain and fatigue were associated to higher Concerns (p < 0.001), while a longer disease duration (p < 0.001) and all pharmacological treatments for a rheumatologic disease (p = 0.001) were associated to higher Necessity levels. A high length of disease, a low level of remission, a high number of total medications, the prescription of an Anti-IL6/bDMARDs/tsDMARDs drug, a high level of pain, fatigue and disability identified patients potentially less adherent to pharmacotherapy to be carefully looked after by clinicians.

Effects on Serum Inflammatory Cytokines of Cholecalciferol Supplementation in Healthy Subjects with Vitamin D Deficiency.

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.

Higher body mass index is associated with a lower iloprost infusion rate tolerance and higher iloprost-related adverse events in patients with systemic sclerosis.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasospasm and microvascular involvement. Iloprost (ILO), a prostaglandin analogous, is used for the treatment of SSc-related Raynaud's phenomenon and digital ulcers. The suggested dose is 0.5-2 ng/kg/min for 6-8 h, and the maximum dose is decided upon the patient's tolerance. Objectives: This study aims to analyze ILO infusion tolerance and possible predictive factors in patients with SSc. Design: This is a retrospective observational study. Method: We evaluated 113 patients with SSc beginning ILO intravenous (IV) infusion treatment between 2004 and 2021. We assessed the maximum tolerated ILO IV infusion rate, the incidence of adverse events (AEs), and the need for symptomatic therapy during the dose-finding sessions. We collected relevant demographic and medical and employed generalized linear models to assess possible predictors of maximum tolerated ILO infusion rate and AEs and logistic regression to assess predictors of AEs. Results: The median ILO infusion rate at the end of the dose-finding process was 0.88 ng/kg/min [interquartile range (IQR) = 0.37]. We found a significant inverse correlation between ILO infusion rate and body mass index (BMI) at the beginning of treatment. BMI was negatively associated with ILO infusion rate (ß = -0.21, p = 0.02) after correction for relevant confounding factors. Overweight patients (BMI >26) presented a 13-fold increased risk of developing AEs during ILO titration [adjusted odds ratio = 13.979, 95% confidence interval (CI) = 2.359-82.845]. AEs during ILO titration occurred in 47.8% of patients, of whom 22.2% presented hypotension. Other AEs were headache, nausea, vomiting, diarrhea, and edema. Symptomatic therapy was needed in half of the patients at least once. Conclusion: This study showed that higher BMI was statistically associated with lower ILO infusion rate tolerance and higher AEs rate, underlying a possible BMI-dependent endothelial dysfunction. Individual ILO regimens still need to be tailored to the patient. Plain Language Summary: Introduction: Systemic sclerosis is a rare a rheumatic disease characterized by skin thickening, vasospasm, and digital ulcers (DUs), as well as other organs involvement. Iloprost, which is administered as intravenous infusion, is one of the main treatments for this disease, and it is effective in reducing vasospasm and the frequency of DUs. Even if there is a suggested dose range, the exact dose must be tailored on each patient, because the tolerance to the drug is variable. Tolerance is limited by dose-dependent unwanted effects, as headache, low blood pressure, dizziness, and sickness. This study aimed to identify possible predictors of such tolerance.Materials and Methods: We collected data from our patients with systemic sclerosis beginning the treatment with iloprost between January 2004 and November 2021 at our hospital facility in Verona, Italy, and analyzed different factors that could be associated with a better tolerance, as age, sex, disease duration, smoking habit, body mass index (a measure of body fatness), blood pressure, concomitant medications, and different patterns of the disease.Results: We found that a higher body mass index was associated with lower iloprost tolerance and higher adverse events rate in patients with systemic sclerosis, while we did not find a correlation with other factors. We believe overweight and obese patients (who have a higher body mass index) have a defect in the vasodilatation mechanism and can therefore be more susceptible to the effect of this medication.Conclusions: While preliminary, our results could provide a good starting point to develop a predictive tool to limit adverse events during this therapy.

Effectiveness and safety of secukinumab in axial spondyloarthritis: a 24-month prospective, multicenter real-life study.

Objectives: To evaluate, in a multicentric Italian cohort of axial spondyloarthritis (axSpA) patients on Secukinumab (SEC) followed for 24 months: (1) the long-term effectiveness and safety of SEC; (2) the drug retention rate and low disease activity (LDA) measured as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 4/Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 and very low disease activity (VLDA) measured as BASDAI < 2/ASDAS < 1.3; (3) any differences in outcomes according to line of biological treatment (naïve/non-naïve), gender (male/female), subtype of axSpA [radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)]. Methods: Consecutive axSpA patients treated with SEC were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical-values were recorded at baseline (T0), 6 (T6), 12 (T12), and 24 (T24) months. Effectiveness was evaluated over-time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug discontinuation and LDA at T6. Infections and adverse events were recorded. Results: A total 249 patients (47.8% male; median age 51) were enrolled; 40.9% had HLA-B27; 53.8% had r-axSpA, and 46.2% nr-axSpA. SEC was prescribed in 28.9% naïve and in 71.1% non-naïve patients. SEC effectiveness was shown as an improvement in several outcomes, such as ASDAS [T0 = 3.5 (2.9-4.4) versus T24 = 1.9 (1.2-2.4); p = 0.02] and BASDAI [T0 = 6.5 (5.0-7.5) versus T24 = 2.8 (1.8-4.0); p = 0.03]. At T24, naïve patients showed better physical functioning and lower disease activity than non-naïve. After 24 months of treatment, 90.7% of naïve and 75.3% of non-naïve patients achieved LDA (BASDAI < 4). Treatment was discontinued in 24.5% patients, mainly due to primary/secondary loss of effectiveness, and in 6.8% due to adverse events. Retention rate at T24 was 75% in the whole population, with some difference depending on gender (p = 0.002). Conclusion: In a real-life clinical setting, SEC proved to be safe and effective in axSpA, mainly in naïve-patients, with a notable drug retention rate. No differences were observed between r-axSpA and nr-axSpA.

Rheumatoid arthritis and myasthenia gravis: a case-based review of the therapeutic options.

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.