Laurent Chiche

Background: Management of systemic lupus erythematosus (SLE) is largely guided by organ involvement. Serositis affects up to 46% of patients, yet its treatment is mainly empirical and extrapolated from other manifestations, and long-term outcome data remain limited. We aimed to evaluate short-term response to anti-inflammatory therapy and to examine associations between immunosuppressive treatments and serositis relapse. Methods: We conducted a multicentre retrospective real-world study in patients with SLE with pericarditis and/or pleuritis, identified through a nationwide call for case reporting. Initial response was defined as symptom and sign resolution at early reassessment. Relapse was defined as recurrence requiring treatment intensification ≥3 months after the index flare. Relapse-free survival was described by Kaplan–Meier methods and analysed as recurrent events using a Prentice-Williams-Peterson gap-time Cox model adjusted for prespecified confounders. Results: One hundred patients contributed 180 serositis episodes (161 pericarditis, 51 pleuritis, associated in 32 cases) over a mean follow-up of 91 months; 46% experienced ≥1 relapse. Overall, 108/124 (87.1%) of evaluable episodes responded to initial anti-inflammatory therapy, with no significant difference between corticosteroid-based and aspirin/colchicine regimens. Corticosteroid use was not associated with increased relapse risk (46.0% vs 46.2%, p=0.98). Conventional immunosuppressants (methotrexate, azathioprine, mycophenolate mofetil) were not associated with reduced relapse risk, whereas belimumab was associated with lower relapse risk (HR=0.34, 95% CI 0.14 to 0.84; p=0.019). Conclusion: Lupus-related serositis is frequent and highly relapsing. In this national cohort, belimumab—but not conventional immunosuppressants—was associated with reduced serositis recurrence, supporting its further evaluation in lupus serositis.

Objective: To assess differences in perception between patients and physicians regarding the determinants of the burden of systemic lupus erythematosus (SLE) in France. Methods: An online survey was conducted by IPSOS, a market research company, among adult patients with SLE and physicians (internists, rheumatologists, nephrologists, and dermatologists) involved in SLE care. The questionnaires were designed by a committee of lupus experts and patient research partners to cover key areas: symptoms experienced by patients with SLE, social and economic impact of the disease, and needs and expectations for the improvement of care pathways. Most questions were formulated to assess comparatively how they were perceived by patients and physicians. Results: Responses from 107 patients and 101 physicians were analyzed. Regarding experienced symptoms, a patient‐physician discordance was observed on the number of reported symptoms ( P < 0.001) and in terms of prioritization, especially with the impact of extreme fatigue (76% vs 51%; P < 0.001) and anxiety and depression (45% vs 13%; P < 0.001), even outside flare‐up periods. Physicians rarely reported that SLE significantly impacts all areas of their patients’ lives, including physical, psychological, social, professional, sexual, and emotional aspects, whereas most patients expressed a lack of medical advice on areas such as sexual and emotional health, family life, professional life, and anxiety. Most patients also declared a perceived lack of information about treatment adverse effects, available therapeutic options, and potential causes of SLE. Conclusion: This survey highlights the significant patient–physician discordances about the burden of SLE in France and supports the need for specific interventions to improve patient information and holistic care.

Objectives: Few recent epidemiological data are available on the risks of chronic kidney disease (CKD), cardiovascular events and infections, in patients with LN, even though these data are crucial for guiding therapeutic decisions. We conducted a cohort study with the aim of evaluating survival without CKD and adverse events in patients with LN. Methods: All patients with a first flare of biopsy-proven LN between 2001 and 2022 followed-up in the University Hospital of Marseille, France, were included in MassiLUP. Patient survival, survival without CKD stages 3, 4 and 5, without cardiovascular event, without severe infection (hospitalization or zoster) and without cancer were assessed. Results: One hundred and sixty-eight patients (82.7% female) were included, mean follow-up was 9.6 ± 5.7 years. Most patients had class III or IV (+/−V) LN. Four patients died (three severe infections and one stroke); 41 (24.4%) patients developed CKD, among whom 19 (11.3%) reached ESKD; 34 (20.2%) patients presented a cardiovascular event, 59 (35.1%) a severe infection and 12 (7.1%) a cancer. Survival rates without CKD were 82.9% and 74.6% at 5 and 10 years; without cardiovascular event were 85.7% and 77.3% at 5 and 10 years; without severe infection were 76.3% and 63.8% at 5 and 10 years; without cancer were 96.3% and 92.9% at 5 and 10 years. Conclusion: Despite free access to treatment and care in France, the long-term prognosis of patients with LN remains burdened both by the risk of CKD, and the risks of cardiovascular and infectious events.

Objective: The SEMAPHORE trial evaluated the efficacy and safety of tocilizumab (TCZ) in glucocorticoid (GC)‐dependent polymyalgia rheumatica (PMR). TCZ reduced GC use and disease activity at 24 weeks.This study aimed to assess relapse rates after stopping TCZ in patients achieving remission at week 24.Methods: In the randomized study, 101 patients received intravenous TCZ (8 mg/kg) or placebo for 24 weeks. Of the 49 TCZ‐treated patients, 33 achieved the primary outcome (PMR‐activity score th week, and two of the remaining 26 subjects (7.7%) sustained remission in the following 6 months. 24 (92.3%) of the total patients experienced relapse. The median time to relapse was 15 weeks (interquartile range: 8–25).Conclusion: Among patients with GC‐dependent PMR, in remission after a 6‐month TCZ treatment, only a minority of the patients remained relapse‐free after TCZ discontinuation. This study suggests that a 6‐month treatment course is not a long enough to withdraw the TCZ. Further studies are needed to determine the optimal TCZ treatment duration and strategies for cessation to prevent relapses.

Objective: Systemic lupus erythematosus (SLE) can negatively impact patients’ social participation. The aim of this study was to identify the determinants of social participation in patients with SLE. Methods: A cross-sectional evaluation was carried out in 100 adult outpatients with SLE enrolled in the multicentre psychosocial lupus (Psy-LUP) study. Participants completed the following standardised questionnaires: Participation Scale (social participation); Zimbardo Time Perspective Inventory; Sarason’s Social Support Questionnaire; Couples Satisfaction Index; Brief Illness Perceptions; Short Form-36 and Lupus-QoL. Stepwise multivariate regression analysis identified determinants of social participation. Results: 92 women and eight men were included. Mean age was 44 years, mean SLE duration was 14 years, 52% of patients had a history of lupus nephritis and 38% were currently receiving immunosuppressants and/or biologics. 73% were in a couple and 64% were employed. Social participation was reduced in 29% of patients (compared with 46% in rheumatoid arthritis or multiple sclerosis), who reported different illness perceptions than those with preserved social participation. In multivariate linear regression, female sex (p=0.006), smoking (p=0.04), osteoporotic fractures (p=0.03), anti-cardiolipin antibodies (p=0.01) and ‘Past Negative’ time perspective (p=0.002) were associated with reduced social participation, while haematological involvement (p=0.005) and ‘Present Hedonistic’ time perspective (p=0.02) were protective. Reduced social participation was also associated with illness representations and with lower health-related quality of life (HR-QoL) scores. Conclusions: Social participation is frequently altered in patients with SLE and correlates with illness representations, time perspective and HR-QoL. Psychological support and therapeutic education may help improve patients’ time perspective. Trial registration number: NCT03913754.

Background: Immune checkpoint inhibitors (ICIs) are responsible for causing immune-related adverse events (irAEs). The frequency and severity of irAEs depend on various factors, but the role of the molecule used remains unclear. Our aim was to assess the comparative safety profile of different programmed cell death-1 inhibitors (anti-PD1) and programmed cell death ligand-1 inhibitors (anti-PD-L1) in a real-life setting. Methods: The occurrence of severe irAEs (grade ≥ 3) and their characteristics were recorded for all patients treated with anti-PD1 or anti-PD-L1, alone or in combination, at our center. Potential predictive factors for the occurrence of irAEs, particularly concerning the type of molecule, were identified by statistical analysis. Factors related to overall survival were also analyzed. Results: A total of 406 patients who received at least one dose of anti-PD1 (68.5%) or anti-PD-L1 (31.5%) were included, among which 60% had lung cancer. The overall frequency of the different ICIs was 51%, 17.5%, 14.3%, 12.8%, and 4.4% for pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab, respectively. Fifty-three (13%) patients experienced severe irAEs (grade 3 or 4). While there were no significant differences with regard to ICI categories (13.7% for anti-PD1 vs 11.7% for anti-PD-L1; p = 0.5878), the rates of severe irAEs were significantly different between ICIs (29.6% for nivolumab, 22.2% for avelumab, 13.8% for atezolizumab, 8.2% for pembrolizumab, and 5.8% for durvalumab; p < 0.0001). Multivariate analyses showed that treatments with nivolumab and low polymorphonuclear neutrophil level were significant risk factors for severe irAEs. The risk of early death was lower in patients who reported severe irAEs and the risk of cancer progression was greater with one of the least toxic molecules (atezolizumab). Discussion: This study highlights the differences in toxicity profile of various ICIs targeting the PD1/PD-L1 axis in real-life use, as well as the identification of possible predictive biomarkers.

Rationale: Associations of autoimmune diseases are rare but interesting and challenging situations from a diagnostic, pathophysiological, and therapeutic point of view. This article studies a rare association of autoimmune diseases by discussing the pathophysiological hypotheses and an original therapeutic management. The coexistence of antineutrophil cytoplasmic antibody-associated vasculitis and spondyloarthritis has rarely been described. Patient concerns: We present a patient with inflammatory back pain, stiffness, and enthesopathies followed by pulmonary and ear, nose and throat granulomatous involvement. Diagnoses: A combination of spondyloarthritis and granulomatosis with polyangiitis, with spinal, enthesopathic, pulmonary, and ear, nose and throat involvement. Interventions and outcomes: Effective treatment with rituximab both on spondyloarthritis and vasculitis. Lessons: We discuss the pathogenic, diagnostic, and therapeutic implications of this rare but intriguing association between these 2 inflammatory conditions.