Role of targeted therapies in rheumatic patients on COVID-19 outcomes: results from the COVIDSER study.

OBJECTIVES: To analyse the effect of targeted therapies, either biological (b) disease-modifying antirheumatic drugs (DMARDs), targeted synthetic (ts) DMARDs and other factors (demographics, comorbidities or COVID-19 symptoms) on the risk of COVID-19 related hospitalisation in patients with inflammatory rheumatic diseases. METHODS: The COVIDSER study is an observational cohort including 7782 patients with inflammatory rheumatic diseases. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Antirheumatic medication taken immediately prior to infection, demographic characteristics, rheumatic disease diagnosis, comorbidities and COVID-19 symptoms were analysed. RESULTS: A total of 426 cases of symptomatic COVID-19 from 1 March 2020 to 13 April 2021 were included in the analyses: 106 (24.9%) were hospitalised and 19 (4.4%) died. In multivariate-adjusted models, bDMARDs and tsDMARDs in combination were not associated with hospitalisation compared with conventional synthetic DMARDs (OR 0.55, 95% CI 0.24 to 1.25 of b/tsDMARDs, p=0.15). Tumour necrosis factor inhibitors (TNF-i) were associated with a reduced likelihood of hospitalisation (OR 0.32, 95% CI 0.12 to 0.82, p=0.018), whereas rituximab showed a tendency to an increased risk of hospitalisation (OR 4.85, 95% CI 0.86 to 27.2). Glucocorticoid use was not associated with hospitalisation (OR 1.69, 95% CI 0.81 to 3.55). A mix of sociodemographic factors, comorbidities and COVID-19 symptoms contribute to patients' hospitalisation. CONCLUSIONS: The use of targeted therapies as a group is not associated with COVID-19 severity, except for rituximab, which shows a trend towards an increased risk of hospitalisation, while TNF-i was associated with decreased odds of hospitalisation in patients with rheumatic disease. Other factors like age, male gender, comorbidities and COVID-19 symptoms do play a role.

Prevalence of ischemic complications in patients with giant cell arteritis presenting with apparently isolated polymyalgia rheumatica.

OBJECTIVE: To investigate the frequency and type of giant cell arteritis (GCA)-related ischemic complications in a series of patients with GCA who, for a substantial period of time (i.e., at least 3 mo), lacked vascular symptoms and presented with apparently isolated polymyalgia rheumatica (PMR). METHODS: Retrospective follow-up study of an unselected population of 167 patients with GCA diagnosed from 1985 to 2014. RESULTS: In all, 18 patients (11%) developed GCA on a background of a prior history of PMR. They were diagnosed as having isolated PMR because they did not have clinical evidence of GCA at diagnosis and exhibited a prompt and complete response to low-dose steroid therapy. However, during the course of treatment, 17 patients later experienced an arteritic relapse with the development of typical craniofacial symptoms, and one patient developed signs of upper extremity vascular insufficiency, resulting in the diagnosis of large-vessel GCA. The median time to GCA diagnosis from the initiation of low-dose steroid therapy was 9 ± 14.4 mo (range: 3-39). At the time of GCA diagnosis, severe ischemic complications were observed in 50% (9/18) of the patients. Of these patients 22% (4/18) were considered to have "true" occlusive disease (i.e., permanent visual loss, stroke, and/or limb claudication). Late inflammation of the aorta and its branches occurred in 4 (22%) of the patients during long-term follow-up. CONCLUSION: Patients with GCA presenting with apparently isolated PMR have a significant risk of developing transient or permanent disease-related ischemic complications; these complications occurred in 50% of the cases.

Biological agents in the management of Felty's syndrome: a systematic review.

OBJECTIVE: To review and summarize the information available on the effectiveness and safety of biological therapies in refractory Felty's syndrome (FS). METHODS: We describe a case of FS with severe neutropenia and recurrent bacterial infections unresponsive to disease-modifying antirheumatic drug treatment and long-term administration with granulocyte colony-stimulating factor, in which treatment with rituximab (RTX) was useful and resulted in a sustained neutrophil response. Current evidence on the use of biological therapies in FS is also analyzed through a systematic review of the English-language literature, based on a PubMed search. RESULTS: Available data on the use of biological therapies in refractory FS are based only on several case reports and are limited to the use of RTX and some anti-tumor necrosis factor α agents (etanercept, infliximab, and adalimumab). Including the case described here, data are available on 8 patients treated with RTX. A sustained increase in the absolute neutrophil count (>1500/mm(3)) was observed in 62.5% (5/8) of these patients after 1 cycle of treatment. In most of them, the hematological response was accompanied by a parallel improvement in biological markers of inflammation and other clinical manifestations of FS (arthritis, recurrent infections, systemic symptoms, etc). After a median follow-up of 9 months (range, 6-14), only 1 of these patients relapsed and neutropenia reappeared; in this patient, retreatment was rapidly effective. No significant adverse events related to RTX therapy were reported. Experience with anti-tumor necrosis factor agents is limited to 6 patients, none of whom presented any sustained increase in neutrophil count. CONCLUSIONS: Although it is not yet possible to make definite recommendations, the global analysis of all cases reported to date only supports the use of RTX as a second-line therapy in patients with refractory FS.

Rituximab therapy in refractory neuropsychiatric lupus: current clinical evidence.

OBJECTIVE: To review and summarize published information on the effectiveness and safety of rituximab (RTX) in adult patients with refractory neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: We describe a patient with persistently active NPSLE, despite conventional therapy, who responded dramatically to RTX. Current evidence on the therapeutic use of RTX in this complex situation is also analyzed through a systematic review of the English-language literature, based on a PubMed search. RESULTS: Available data on the use of RTX in refractory NPSLE come from a large number of case reports and some open-label studies. Including our case, 35 patients have been well documented. A complete or partial therapeutic response was achieved in 85% of patients after 1 cycle of treatment. A positive correlation between serological markers of disease activity and clinical outcome has also been demonstrated in some of these patients. Clinical improvement was accompanied by a significant reduction in the daily dose of oral corticosteroids. Relapse after RTX treatment was noted in 45% of cases (median 9.5 months; range, 4-33 months). Infections were observed in 29% of patients. CONCLUSION: Evidence for the effectiveness of RTX as induction therapy in NPSLE is based solely on several case reports and noncontrolled trials. Although it is not yet possible to make definite recommendations, the global analysis of these cases supports the off-label use of RTX in cases of severe refractory NPSLE.