Clinical and peculiar immunological manifestations of SARS-CoV-2 infection in systemic lupus erythematosus patients.

OBJECTIVES: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with SLE remains unclear and data on clinical manifestations after infection are lacking. The aim of this multicentre study is to describe the effect of SARS-CoV-2 in SLE patients. METHODS: SLE patients referring to four Italian centres were monitored between February 2020 and March 2021. All patients with SARS-CoV-2 infection were included. Disease characteristics, treatment, disease activity and SARS-CoV-2-related symptoms were recorded before and after the infection. RESULTS: Fifty-one (6.14%) SLE patients were included among 830 who were regularly followed up. Nine (17.6%) had an asymptomatic infection and 5 (9.8%) out of 42 (82.6%) symptomatic patients developed interstitial pneumonia (no identified risk factor). The presence of SLE major organ involvement (particularly renal involvement) was associated with asymptomatic SARS-CoV-2 infection (P = 0.02). Chronic corticosteroid therapy was found to be associated with asymptomatic infection (P = 0.018). Three SLE flares (5.9%) were developed after SARS-CoV-2 infection: one of them was characterized by MPO-ANCA-positive pauci-immune crescentic necrotizing glomerulonephritis and granulomatous pneumonia. CONCLUSIONS: SARS-CoV-2 infection determined autoimmune flares in a small number of patients. Our data seem to confirm that there was not an increased risk of SARS-CoV-2 in SLE. Patients with asymptomatic SARS-CoV-2 infections were those having major SLE organ involvement. This may be explained by the high doses of corticosteroids and immunosuppressive agents used for SLE treatment.

Patient Perception of Depressive Symptoms in Rheumatic Diseases: A Cross-sectional Survey.

OBJECTIVES: The presented study aimed to explore the presence and the self-identification of depressive symptoms among patients with rheumatic musculoskeletal diseases (RMDs) through the use of the Patient Health Questionnaire (PHQ-9). METHODS: Between June and October 2019, patients from the regional association for people with RMDs in Lombardy, Italy (ALOMAR), were invited to participate in a cross-sectional online survey. Participants completed PHQ-9 along with a survey about their perception of depressive symptoms. Patients were stratified according to PHQ-9 score as follows: not depressed (<4), subclinical or mild depression (5-9), moderate depression (10-14), moderately severe depression (10-14), and severe depression (20-27). Descriptive statistics and analyses of variance were used to explore data. RESULTS: Of the 192 RMD patients who completed PHQ-9, 35 (18.2%) were not depressed, 68 (35.4%) had subclinical or mild depression, 42 (21.9%) had moderate depression, 30 (15.6%) had moderately severe depression, and 17 (8.9%) had severe depression. Contrary to the above findings, only 16 respondents (8.3%) reported that they experienced depressive symptoms, and only 7 of the 16 were being followed by a psychiatrist. Respondents with higher PHQ-9 scores tended to have concomitant fibromyalgia, to be younger, and to be overweight. CONCLUSIONS: The current results indicate the overall burden of depressive symptoms in RMD patients. While clinical depression (PHQ-9 >10) was detected in 41.2% of respondents, only 8.3% reported that they experience depressive symptoms. Routine screening of RMD patients for depression is therefore critical.

Relevant non-pharmacologic topics for clinical research in rheumatic musculoskeletal diseases: The patient perspective.

OBJECTIVE: The research approach on rheumatic musculoskeletal diseases (RMDs) is challenging and patient involvement is an emerging issue to obtain relevant information to research. Despite growing interest in non-pharmacologic aspects of clinical research in RMDs, the patients' perspectives are currently poorly explored. METHODS: A cross-sectional no-profit online survey was devised to identify and rank the priorities for clinical research in RMDs according to patients' perspectives. Patients were asked to rate the following topics: food/nutrition, air pollution, smoking, work activity, social participation, physical activity, emotional well-being/stress, alternative medicine, and patient-physician relationship. The survey was disseminated by ALOMAR (Lombard Association for Rheumatic Diseases) between June and October 2019. RESULTS: Two hundred RMD patients completed the survey. The topic most rated 188 (94%) was the doctor-patient relationship, considered very or extremely important. Other topics rated as follows: psychological well-being 185 (92.5%), physical activity 155 (77.5%), nutrition, eating habits 150 (75%), alternative therapies 144 (72%), work activity 144 (72%), environmental pollution 134 (67%), social life 121 (60.5%) and cigarette smoke 119 (59.5%). The topics considered relevant were perceived to be able to influence disease symptoms. Environmental pollution and smoking were considered the most important for RMD prevention in 43.3% and 48.7% respectively. CONCLUSIONS: This survey highlights the relevance of several unmet needs and indicates that active patient involvement is essential to design successful translational studies and improve clinical outcomes.

Successful sequential therapy with rituximab and belimumab in patients with active systemic lupus erythematosus: a case series.

OBJECTIVES: B cells play an important role in the initiation and progression of systemic lupus erythematosus (SLE). Accordingly, B cell-targeted therapy has been suggested as a new rational approach for treating lupus. Belimumab, a human monoclonal antibody directed against B lymphocyte stimulator (BLyS), was reported as the first biological treatment effective in reducing mild-to-moderate SLE disease activity by using different scoring systems and endpoints. Conversely clinical trials with rituximab, a chimeric monoclonal antibody directed against the CD20 expressed by B cells, have failed to achieve primary endpoints in spite of a number of reports showing its beneficial effects. Anecdotal reports have described the sequential use of rituximab and belimumab as a more effective treatment than using the individual drugs alone, without compromising safety. METHODS: We report a case series of three patients with active SLE refractory to conventional therapies, who underwent treatment with rituximab followed by belimumab as maintenance therapy. RESULTS: We observed a beneficial effect after sequential treatment with rituximab and belimumab. All patients achieved long-standing remission and could reduce or discontinue corticosteroids. Concomitantly, after rituximab administration we observed a rise in BLyS levels, which were dramatically reduced after belimumab introduction. CONCLUSIONS: The modulation of plasma BLyS kinetics in patients undergoing sequential treatment with rituximab and belimumab may represent a possible rationale behind the effectiveness of this combined therapy.

Current perspective on rituximab in rheumatic diseases.

The steadily increasing knowledge regarding pathogenetic mechanisms in autoimmune rheumatic diseases has paved the way to different therapeutic approaches. In particular, the market entry of biologics has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients' quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), first used in the treatment of non-Hodgkin's lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis. Nowadays, in rheumatology, RTX is also used with off-label indications in patients with systemic sclerosis, Sjögren's syndrome and systemic lupus erythematosus. RTX is a monoclonal antibody directed to CD20 molecules expressed on the surfaces of pre-B and mature B lymphocytes. It acts by causing apoptosis of these cells with antibody- and complement-dependent cytotoxicity. As inflammatory responses to cell-associated immune complexes are key elements in the pathogenesis of several autoimmune rheumatic diseases, such an approach might be effective in these patients. In fact, RTX, by promoting the rapid and long-term depletion of circulating and lymphoid tissue-associated B cells, leads to a lower recruitment of these effector cells at sites of immune complex deposition, thus reducing inflammation and tissue damage. RTX is of the most interest to rheumatologists as it represents an important additional therapeutic approach. Thus, the advent in clinical practice of approved RTX biosimilars, such as CT-P10, may be of help in improving treatment access as well as in reducing costs.