Polypharmacy, drug-drug interactions, and adverse drug reactions among systemic sclerosis patients: A cross-sectional risk factor study.

OBJECTIVES: Polypharmacy, drug-drug interactions (DDI) and related adverse drug reaction (ADR) are understudied in SSc. The aim of this work was to determine the prevalence and determinants of DDI and ADR in a real-life prospective cohort of SSc patients. METHODS: We performed a retrospective analysis of the drug prescriptions of SSc patients admitted to the daily scleroderma clinic between January 2020 and April 2022. DDI were identified using 2 prescription analysis applications, and adjudicated related ADRs occurring during a one-year follow-up were reported. Risk factors for DDI and ADR were identified using multivariate analysis. RESULTS: One hundred and eight SSc patients were included. The median number of medications per patient was 6 [4-9]. Seventy-one (65.7 %) patients had 5 or more medications, and 23 (21.3 %) had 10 or more. Seventy-two (66.7 %) patients had DDIs on their prescriptions at inclusion. Patients with DDIs had more medications than patients without DDIs (7 [5-10] versus 3 [2-5], p < 0.0001). Six (8.3) patients experienced ADRs during the one-year follow-up. Patients with ADRs had more medications (14 [10-18] versus 7 [5-10] p < 0.001) and more DDIs (12 [7-32] versus 3 [1-6]; p < 0.001) than patients without ADRs. Multivariate analysis confirmed that the number of prescribed medications was independently positively associated with DDIs (OR: 2.25 [1.52-3.32], p < 0.0001) as well as with ADRs (OR: 1.68 [1.17-2.40], p < 0.01). CONCLUSIONS: SSc patients are significantly exposed to polypharmacy, DDIs and related ADRs, particularly in cases of severe illness, and especially if 5 or more medications are prescribed.

[18F]FDG PET/CT for therapeutic assessment of Abatacept in early-onset polymyalgia rheumatica.

PURPOSE: Evaluate the benefit of 2-deoxy-2-[18F]-fluoro-D-glucose ([18F] FDG) positron emission tomography/computed tomography (PET/CT) for the therapeutic assessment of Abatacept (ABA) as first-line therapy in early-onset polymyalgia rheumatica (PMR) patients. METHODS: This was an ancillary study of ALORS trial (Abatacept in earLy Onset polymyalgia Rheumatica Study) assessing the ability of ABA versus placebo to achieve low disease activity (C-Reactive Protein PMR activity score (CRP PMR-AS) ≤ to 10) without glucocorticoid (GC) at week 12 in patients with early-onset PMR. The patients underwent [18F] FDG PET/CT at baseline and after 12 weeks of treatment. Responses to treatments were evaluated according to CRP PMR-AS, Erythrocyte Sedimentation Rate (ESR) PMR-AS, Clin PMR-AS, and CRP-Imputed (Imput-CRP) PMR-AS. Quantitative score by maximal standardized uptake value (SUVmax) and combined qualitative scores according to liver uptake (Leuven, Leuven/Groningen, and Besançon Scores) were used for assessment of [18F] FDG uptake in regions of interest (ROI) usually affected in PMR. Student's t-test was applied to evaluate the clinical, biological, and [18F] FDG uptake variation difference in ABA and placebo groups between W0 and W12. Subgroup analysis by GC rescue was performed. RESULTS: At W12, there was no significant difference according to SUVmax between the ABA and the placebo groups in all ROI. Subgroup analysis according to GC administration demonstrated a significant (p 0.047) decrease in SUVmax within the left sternoclavicular joint ROI in the ABA group (- 0.8) compared to the placebo group (+ 0.6) without GC rescue. Other results did not reveal any significant difference between the ABA and placebo groups. According to combined qualitative scores, there was no significant difference between ABA and placebo groups for the direct comparison analysis and subgroup analysis according to GC rescue. CONCLUSION: [18F] FDG PET/CT uptake did not decrease significantly after ABA compared to placebo in anatomical areas usually affected in PMR patients. These results are correlated with the clinical-biological therapeutic assessment. CLINICAL TRIAL REGISTRATION: The study was approved by the appropriate ethics committee (CPP Sud-Est II Ref CPP: 2018-33), and all patients gave their written informed consent before study enrollment. The protocol was registered on Clinicaltrials.gov (NCT03632187).

Obinutuzumab as treatment for ANCA-associated vasculitis.

OBJECTIVES: Rituximab is a standard of care therapy for patients with ANCA-associated vasculitis. When rituximab is contraindicated, or in the case of refractory disease, other treatments are needed. Obinutuzumab is another anti-CD20 antibody for the treatment of haematological malignancies that may induce a deeper B cell depletion compared with rituximab. This article reviews three cases of patients with ANCA-associated vasculitis who were treated with obinutuzumab due to their history of anaphylactic reactions to rituximab. METHODS: Case series of three patients with ANCA-associated vasculitis treated with obinutuzumab. RESULTS: One female patient with microscopic polyangiitis and two male patients with granulomatosis with polyangiitis received obinutuzumab. The treatment was well-tolerated in all patients despite previous anaphylactic reaction to rituximab. Treatment with obinutuzumab was effective in (i) inducing disease remission, (ii) inducing total B cell depletion, and (iii) resulting in undetectable serum titres of ANCA. All three patients were re-treated with obinutuzumab for maintenance of remission. CONCLUSION: Obinutuzumab appears to be a safe and efficacious therapy for patients with ANCA-associated vasculitis who have had refractory disease or a history of anaphylaxis to rituximab. Prospective studies comparing rituximab to obinutuzumab in ANCA-associated vasculitis patients are warranted.

The pathophysiology of polymyalgia rheumatica, small pieces of a big puzzle.

Polymyalgia rheumatica (PMR) is a frequent rheumatic condition among people over 50 years of age. Despite its frequent association with giant cell arteritis (GCA), PMR can be isolated. Its pathophysiology is poorly understood. Nevertheless, many studies are ongoing; 98 studies are currently referenced in ClinicalTrials.org involving several conventional and targeted therapies. In this review, we synthetize the current knowledge about PMR pathophysiology according to genetic and immunogenetic, immunologic, antibody and aging data. Immunogenetic data are mainly related to the HLA system and the association between the HLA-DRB1 and PMR. Few studies are also about immunogenetics of proinflammatory interleukins (i.e. IL-6). The decrease of CD8+Tcells and the strong increase of IL-6 where the main elements of PMR's pathophysiology until the recent years. The disturbance of B cell homeostasis, the search for IL-6 secretion by the innate immune system, the role of aging, are new elements revealed by recent studies. Aging might be a key element to consider as PMR occurs in patients over 50 years of age. Aging may act by the increased susceptibility to infections, by immunological modifications or hormonal disturbances. The role of the cellular infiltration around the joints remains a crucial question. Only a handful of studies described this infiltration. Finally, this review reveals the gaps in available data and suggests new leads and in-depth studies for further research on PMR pathophysiology.

Lung involvement in ANCA-associated vasculitis.

Lung involvement is one of the most common clinical features in ANCA-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In this review, we detail the five main presentations of pulmonary involvement in AAV: necrotizing granulomatous inflammation, tracheobronchial inflammation, pulmonary capillaritis, interstitial lung disease (ILD) and asthma with their clinical, radiological and therapeutic characteristics. The prevalence of these manifestations is variable according to the subtype of AAV, necrotizing granulomatous inflammation and tracheobronchial inflammation being defining features of GPA whereas ILD is primarily seen in patients with MPA, especially in association with ANCA directed against myeloperoxydase (MPO-ANCA), and asthma is characteristic of EGPA. Despite recent progresses in the diagnosis and management of these conditions, several questions remain and are discussed here, including local treatments for subglottic stenosis, the uncertain efficacy of plasma exchanges for alveolar hemorrhage, the potential role of antifibrotic agents in ILD associated with MPA, and the use of novel anti-IL-5 strategies in EGPA.

Eosinophilic granulomatosis with polyangiitis: the multifaceted spectrum of clinical manifestations at different stages of the disease.

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) usually occurs in patients with late-onset asthma and sustained peripheral blood eosinophilia and classically presents with a clinical multifaceted spectrum of manifestations, which may vary at the different stages of the natural history of the disease.Areas covered: We reviewed EGPA clinical presentation, focusing on clinical manifestations at three different phases of the disease: 1/before the development of overt vasculitis, 2/at vasculitis diagnosis and 3/during the long-term follow-up. An update on current classification criteria and recent therapeutic advances has been provided as well.Expert opinion: Asthma, chronic rhinosinusitis and blood eosinophilia could anticipate the overt vasculitis for years. An atopic background may be present in a subset of patients (25-30%), while ANCA presence varies between 10 and 40%. Systemic vasculitis rapidly occurs and clinical features demonstrating vasculitis processes (neuropathy, purpura, scleritis, alveolar hemorrhage and glomerulonephritis) develop along with systemic symptoms (50%). After vasculitis resolution, asthma remains severe in up to 50% of patients and incidence of isolated-asthma and rhinosinus exacerbations remains constantly high. Different sets of classification criteria have been published so far, and DCVAS diagnostic criteria will be presented soon. Interleukin-5 blockers seem to be promising to control the disease and to spare corticosteroids.