Search

Objective: To investigate survival in Italian systemic sclerosis (SSc) patients from a tertiary center, reporting death causes. Materials and methods: We analyzed the charts of 251 SSc patients prospectively enrolled in our Rheumatology Unit from 2000 to 2008. Baseline characteristics were recorded. In 2008 the vital status and the causes of death were assessed. Overall and subgroup survival were analyzed by the Kaplan-Meier method and the log-rank test. Results: In 2008, 82% of patients were alive, 8% were known to have died and 10% were lost to follow-up. Overall 5- and 8-year survival were 94.8% and 77.1%, respectively. Patients with an age greater than the median value of the cohort (χ2=4.4; p=0.036), diffuse cutaneous SSc (χ2=3.9; p=0.048), digital ulcers (χ2=6; p=0.015), articular (χ2=5.3; p=0.021), lung (χ2=5.6; p=0.018) and heart involvement (χ2=9.3; p=0.002) had a poorer survival than patients without these features. The majority of SSc-related deaths (60%) were secondary to interstitial lung disease and heart involvement (both 33.3%); 50% of non-SSc-related deaths were due to cancer. Conclusions: Our study reports an improvement in survival of Italian SSc patients during the last decade with respect to the previous ones. Moreover, a reduction in deaths from renal involvement and an increase in deaths from interstitial lung disease were recorded in Italian SSc patients. Our data are consistent with those from recent survival studies carried out on SSc patients from other geographic areas.

Objectives: Current guidelines suggest treating poor-prognosis eosinophilic granulomatosis with polyangiitis (EGPA) with a combination of glucocorticoids (GCs) plus cyclophosphamide (CYC). However, there is little data to support the need for the addition of CYC. The objective of this study was to compare GCs plus CYC to GCs alone as induction therapy in poor-prognosis EGPA., Methods: We emulated a target trial using observational data from a European multicenter retrospective database. We included patients with newly diagnosed EGPA with a 1996 Five Factor Score (FFS) of at least 1, treated with GCs or GCs plus CYC between June 1985 and November 2018. Propensity score analysis was used to adjust for potential confounders. Primary outcome was relapse at 12months. Secondary outcomes included major relapse at 12months and GC-dependent asthma and/or ear nose and throat (ENT) manifestations at 24months., Results: A total of 209 patients were included: 47 % were male and the mean age at diagnosis was 52 (±16 years); 26 % were treated with GCs alone and 74 % with GCs plus CYC. After adjustment, the risk of relapse (hazard ratio [HR]: 0.24, 95%CI [0.08-0.67], p = 0.007), major relapse (HR: 0.24, 95%CI [0.07-0.85], p = 0.026) and the proportion of GC-dependent asthma and/or ENT manifestations (odds ratio:0.30, 95%CI [0.14-0.66], p = 0.003) were lower in the GCs plus CYC group compared to the GCs alone group., Conclusion: This target trial emulation study shows that the addition of CYC to GCs reduces the risk of vasculitis relapse and the rate of GC-dependent asthma and/or ENT manifestations in patients with poor-prognosis EGPA., Competing Interests: Declaration of competing interest Dr Terrier reported consulting fees from AstraZeneca, GlaxoSmithKline, CSL Vifor, Novartis, LFB, Boehringer Ingelheim., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Transparent trial conduct requires prospective registration of a randomized controlled clinical trial (RCT) before the enrollment of the first participant. We aimed to (1) estimate the proportion of RCTs that are prospectively registered and analyze the time trends and factors linked to registration timing and (2) assess the reasons for nonadherence to prospective registration and explore ways to improve compliance. We studied trials published in rheumatology as a case study., Study Design and Setting: We searched for RCTs in rheumatology published between 2009 and 2022. We conducted a multivariable logistic regression to identify factors associated with prospective trial registration. We sent a survey to investigators of trials not prospectively registered, asking about reasons for nonadherence and potential solutions., Results: We identified 1093 RCTs; 453 (41.4%) were not prospectively registered. Of these, 130 (11.9%) were not registered and 323 (29.5%) were retrospectively registered. Prospective registration increased by 3% annually (P < .001), with 13.3% (2 of 15) trials registered in 2009 to 73.2% (112 of 153) in 2022. In journals supporting the International Committee of Medical Journals Editors recommendations, 16% of trials published in 2022 were not prospectively registered. Prospective registration was associated with a larger sample size, multinational recruitment, and publication in higher impact journals. Investigators reported lack of knowledge or organizational problems as key reasons for retrospective registration. They suggested linking ethical approval to trial registration to ensure prospective registration., Conclusion: Despite significant improvement, adherence to prospective registration remains unsatisfactory in rheumatology. Targeted strategies for journal editors, health-care professionals, and researchers may help improve trial registration., Plain Language Summary: Randomized controlled clinical trials are a research type where people are randomly assigned to different treatments to see which works best. These treatments can include drugs, surgery, medical devices, or changes in behavior. The results obtained in RCTs are essential for the advance of medicine and for making medical decisions. Randomized controlled clinical trials need to be conducted in a transparent way to provide trustworthy information and avoid misleading findings. A key aspect of transparency is registering the study details and plan in a public repository before the trial starts. This not only requires researchers to plan their study in advance but also enables the scientific community to track any change in how the study is conducted. Although registration of RCTs is recommended, it is not compulsory. Questions remain about researchers' compliance with prospective registration, and the factors that may affect it. In the present study, we systematically studied the registration practices of rheumatology RCTs published between 2009 and 2022. We reviewed how the trials were registered and used a statistical method (multivariable logistic regression) to determine what factors were linked to whether a trial was registered before it started. We also sent a questionnaire to researchers who either did not register or retrospectively registered their study, asking for their suggestions on how to improve adherence to proper registration practices. We found 1093 trials, of which 453 (41.4%) were not registered before they started. Among these, 130 (11.9%) were never registered and 323 (29.5%) were retrospectively registered. Trials with a larger number of participants, those involving recruiting centers from multiple countries, and those published in more prestigious journals were more likely to be registered in advance and adhere to transparency recommendations. Researchers who did not register their trial before it started reported that lack of awareness and organizational issues as the main reasons for not following these recommendations. They suggested that connecting ethical approval to trial registration could be a solution for ensuring adequate registration. We found that even though trial registration has improved in recent years, a considerable number of rheumatology trials are still not registered before they start. Based on our findings, we think that focusing on strategies for journal editors, health-care professionals, and researchers could help increase the number of properly registered trials., Competing Interests: Declaration of competing interest T.A. is the Chair of the Magic Evidence Ecosystem Foundation. M.I. received consulting fees from Boehringer Ingelheim and received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim and CSL Vifor, and has participated in the Advisory Board for Novartis. There are no competing interests for any other author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study is to evaluate whether adding oral glucocorticoids to immunosuppressive therapy improves skin scores and ensures safety in patients with early diffuse cutaneous systemic sclerosis (dcSSc)., Methods: We performed an emulated randomized trial comparing the changes from baseline to 12 ± 3 months of the modified Rodnan skin score (mRSS: primary outcome) in patients with early dcSSc receiving either oral glucocorticoids (≤20 mg/day prednisone equivalent) combined with immunosuppression (treated) or immunosuppression alone (controls), using data from the European Scleroderma Trials and Research Group. Secondary end points were the difference occurrence of progressive skin or lung fibrosis and scleroderma renal crisis. Matching propensity score was used to adjust for baseline imbalance between groups., Results: We matched 208 patients (mean age 49 years; 33% male; 59% anti-Scl70), 104 in each treatment group, obtaining comparable characteristics at baseline. In the treated group, patients received a median prednisone dose of 5 mg/day. Mean mRSS change at 12 ± 3 months was similar in the two groups (decrease of 2.7 [95% confidence interval {95% CI} 1.4-4.0] in treated vs 3.1 [95% CI 1.9-4.4] in control, P = 0.64). Similar results were observed in patients with shorter disease duration (≤ 24 months) or with mRSS ≤22. There was no between-group difference for all prespecified secondary outcomes. A case of scleroderma renal crisis occurred in both groups., Conclusion: We did not find any significant benefit of adding low-dose oral glucocorticoids to immunosuppression for skin fibrosis, and at this dosage, glucocorticoid did not increase the risk of scleroderma renal crisis., (© 2024 American College of Rheumatology.)

Objective: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) primarily affects small vessels. Large-vessel involvement (LVI) is rare. We aimed to describe the characteristics of LVI, to identify associated risk factors, and to describe its therapeutic management., Methods: This multicenter case-control (1:2) study included patients with AAV according to the ACR/EULAR classification and LVI as defined by the Chapel Hill nomenclature, together with controls matched for age, sex, and AAV type., Results: We included 26 patients, 15 (58 %) of whom were men, with a mean age of 56.0 ± 17.1 years. The patients had granulomatosis with polyangiitis (n = 20), or microscopic polyangiitis (n = 6). The affected vessels included the aorta (n = 18; 69 %) supra-aortic trunks (n = 9; 35 %), lower-limb arteries (n = 5; 19 %), mesenteric arteries (n = 5; 19 %), renal arteries (n = 4; 15 %), and upper-limb arteries (n = 2; 8 %). Imaging showed wall thickening (n = 10; 38 %), perivascular inflammation (n = 8; 31 %), aneurysms (n = 5; 19 %), and stenosis (n = 4; 15 %). Comparisons with the control group revealed that LVI was significantly associated with neurological manifestations (OR=3.23 [95 % CI: 1.11-10.01, p = 0.03]), but not with cardiovascular risk factors (OR=0.70 [95 % CI: 0.23-2.21, p = 0.60]), or AAV relapse (OR=2.01 [95 % CI: 0.70-5.88, p = 0.16]). All patients received corticosteroids, in combination with an immunosuppressant in 24 (92 %), mostly cyclophosphamide (n = 10, 38 %) or rituximab (n = 9, 35 %)., Conclusion: Regardless of distinctions based on vessel size, clinicians should consider LVI as a potential manifestation of AAV, with the aorta commonly affected. The risk of developing LVI appears to be greater for clinical phenotypes of AAV with neurological involvement. Standard AAV treatment can be used to manage LVI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: The anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) reported in systemic sclerosis (SSc). Especially due to low prevalence, the clinical relevance of NOR90 in SSc remains uncertain., Objectives: To analyze the clinical associations of NOR90 in patients with SSc in a multicentric cohort., Methods: Post-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) database, with additional information on NOR90. Further, we performed a systematic literature search, using the terms "systemic sclerosis" and "NOR90" across three databases: Medline via PubMed, Scopus, and Thomson Reuters' Web of Science Core Collection, from inception to November 1st, 2023., Results: Overall, 1318 patients with SSc were included (mean age 58.3 ± 13.7 years, 81.3 % female), of whom 44 (3.3 %) were positive for NOR90. Of these, 32 were also positive for one of the SSc-criteria antibodies: 9/44 (20.5 %) for anti-topoisomerase I, 18/42 (42.9 %) for anti-centromere, and 5/40 (12.5 %) for anti-RNA polymerase III. NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal (GI) symptoms compared to NOR90-negative patients. In multivariable analysis, NOR90 remained significantly associated with lower mRSS and less frequent GI symptoms. The literature search identified 17 articles, including a total number of 87 NOR90-positive out of 3357 SSc patients, corresponding to an overall prevalence of 2.6 %., Conclusion: To our best knowledge, this is the largest SSc cohort tested for NOR90 to date, confirming the NOR90 prevalence in SSc patients is around 3 %., Competing Interests: Declaration of competing interest DIMA Alina: Nothing to disclose. VONK Madelon: Consultancy relationship with and/or research funding from and/or speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: Boehringer Ingelheim, Ferrer, Galapagos, GSK, Janssen, MSD and Novartis. GARAIMAN Alexandru: Nothing to disclose. KERSTEN E Brigit: Nothing to disclose. BECVAR Radim: Nothing to disclose. TOMCIK Michal: Nothing to disclose. HOFFMANN-VOLD Anna-Maria: Speakers bureau: Boehringer Ingelheim, Jannsen, Medscape, Merck Sharp & Dohme and Roche; Consultant: ARXX, Boehringer Ingelheim, Genentech, Jannsen, Medscape, Merck Sharp & Dohme and Roche; Grant/research support: Boehringer Ingelheim, Jannsen CASTELLVI Ivan: Speakers’ bureau: Boehringer, Janssen-Cilag, BMS, Roche, UCB; Consultant: Boehringer, Janssen-Cilag, Topandur. TANDAIPAN JAIME Jose Luis: Nothing to disclose. BRZOSKO Marek: Nothing to disclose. MILCHERT Marcin: Nothing to disclose. KRASOWSKA Dorota: Speakers’ bureau: Novartis, Abbvie, Elli Lilly; Consultant: Boehringer Ingelheim, Novartis, Janssen. MICHALSKA-JAKUBUS Małgorzata: Nothing to disclose. AIRO Paolo: Consulting fees, honoraria for lectures, presentations, or educational events, support for attending meetings and/or travel from: Bristol Myers Squibb, Bohringer Ingelheim, Roche, Novartis, CSL Behring Janssen- Cilag MATUCCI-CERINIC Marco: Speakers’ bureau: Biogen, Sandoz, Boehringer, Lilly, Galapagos; Grant/research support: MSD, Janssen; BRUNI Cosimo: Consultant: Boehringer Ingelheim; Grant/research support: Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC); Novartis Foundation for medical-biological research, EMDO Foundation; Educational grants: AbbVie, Wellcome Trust. IUDICI Michele: Nothing to disclose. DISTLER Jorg: Nothing to disclose. GHEORGHIU Ana-Maria: Speakers’ bureau: Sandoz, Boehringer Ingelheim, Ewopharma; Consultant: Boehringer Ingelheim. POORMOGHIM Hadi: Nothing to disclose. MOTTA Francesca: FM had consulting fees from Thermo Fisher. DE SANTIS Maria: Nothing to disclose. PARVU Magda: Nothing to disclose. DISTLER Oliver: OD has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three calendar years: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143). Research Grants: BI, Kymera, Mitsubishi Tanabe MIHAI Carina: CM received consulting fees and/or honoraria from Boehringer Ingelheim, Janssen Cilag AG, MED Talks Switzerland, Medbase, Mepha, Novartis, and PlayToKnow AG, and congress support from Boehringer Ingelheim and Roche., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate whether the efficacy and safety data from drug-registration trials can be extrapolated to real-life RA patients receiving RTX., Methods: The 'AutoImmunity and Rituximab' (AIR-PR) registry is a French multicentre, prospective cohort of RA patients treated with RTX in a real-life setting. We compared treatment responses at 12 months and serious adverse events (AEs) between eligible and non-eligible patients, by retrieving the eligibility criteria of the three rituximab-registration trials. We determined critical eligibility criteria and modelled the benefit-risk ratio according to the number of fulfilled critical eligibility criteria., Results: Among 1984 RA patients, only 9-12% fulfilled all eligibility criteria. Non-eligible patients had fewer EULAR responses at 12 months (40.3% vs 46.9%, P = 0.044). Critical inclusion criteria included swollen joints count ≥4, tender joints count ≥4, CRP ≥15 mg/l and RF positivity. Critical exclusion criteria were age >80 years, RA-associated systemic diseases, ACR functional class IV, DMARD other than MTX and prednisone >10 mg/day. Only 20.8% fulfilled those critical eligibility criteria. During the first year, serious AEs occurred for 182 (9.2%) patients (70.3% serious infections) and patients with ≥1 critical exclusion criterion were at higher risk (hazard ratio 3.03; 95% CI 2.25-4.06; for ≥3 criteria vs 0). The incremental risk-benefit ratio decreased with the number of unmet critical inclusion criteria and of fulfilled exclusion criteria., Conclusion: Few real-life RA patients were eligible for the drug-registration trials. Non-eligible patients had lower chance of response, and higher risk of serious AEs. Efficacy and safety data obtained from those trials may not be generalizable to RA patients receiving RTX in real-world clinical practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Early diagnosis and prompt initiation of treatment are crucial to avoid severe complications in giant cell arteritis (GCA). The European Alliance of Associations for Rheumatology (EULAR) recommendations for the use of imaging in large vessel vasculitis have helped better define the role of different techniques for diagnosing and monitoring the disease. Regarding the treatment, corticosteroids remain the standard, and tocilizumab is the preferred corticosteroid-sparing treatment. New corticosteroid-sparing treatments and "ultra-light" corticosteroid usage regimens are also under study and could represent valid therapeutic alternatives in the future., Competing Interests: M. Iudici est impliqué dans des études cliniques sponsorisées par Novartis et Merck. La seconde auteure n’a déclaré aucun conflit d’intérêts en relation avec cet article.

Objectives: Systemic sclerosis is a chronic autoimmune connective tissue disease leading to microvascular and fibrotic manifestations in multiple organs. Several treatment options and recommendations from different European countries are available. In this study, for which the ambit is Switzerland specifically, we aim to describe the treatment patterns of systemic sclerosis patients with fibrotic manifestations., Methods: Systemic sclerosis patients were selected from six Swiss tertiary centres recorded in the multicentre, prospective European Scleroderma Trials and Research (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR systemic sclerosis classification criteria at baseline were included. To determine the differences in treatment of varying degrees of fibrosis, four groups were identified: (1) patients with a modified Rodnan skin score (mRSS) >0; (2) those with mRSS ≥7; (3) those with interstitial lung disease (SSc-ILD), diagnosed by either chest X-Ray or high-resolution computed tomography; and (4) patients fulfilling one of the additional criteria for extensive interstitial lung disease, defined as interstitial lung disease involvement of >20% in high-resolution computed tomography, dyspnea NYHA-stage 3/4, or a predicted forced vital capacity (FVC) of <70%., Results: A total of 590 patients with systemic sclerosis fulfilled the inclusion criteria. In this cohort, 421 (71.4%) had mRSS >0, of whom 195 (33.1%) had mRSS ≥7; interstitial lung disease was diagnosed in 198 of 456 (43.4%), of whom 106 (18.0 %) showed extensive interstitial lung disease. Regarding non-biologic disease-modifying medications (DMARDs), the most frequently prescribed was methotrexate, followed by hydroxychloroquine and mycophenolate mofetil. Rituximab and tocilizumab were most frequently used among the biologic DMARDs. Specifically, 148/372 (39.8%) of treated patients with skin fibrosis received methotrexate, mycophenolate mofetil or rituximab, and 80/177 (45.2%) with interstitial lung disease received cyclophosphamide, mycophenolate mofetil, tocilizumab or rituximab. Most patients received a proton-pump inhibitor, and few patients underwent hematopoietic stem cell transplantation., Conclusion: Overall, in Switzerland, a wide range of medications is prescribed for systemic sclerosis patients. This includes modern, targeted treatments for which randomised controlled clinical trial have been recently reported.

In rheumatology, this year has been characterized by a broader knowledge of the pathogenesis of rheumatoid arthritis and mechanisms involved in the onset and persistence of low back pain. Studies relevant to the management of of gout, axial spondyloarthritis, autoinflammatory diseases and systemic vasculitides were published. New data on the safety of JAK inhibitors have been published. The ASAS-EULAR recommendations for the treatment of axial spondyloarthritis were updated, and the 2023 EULAR/PReS guidelines for the diagnosis and treatment of systemic juvenile idiopathic arthritis and adult-onset Still's disease are now available. New molecules and different glucocorticoid sparing strategies were introduced for giant cell arteritis., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objective: To identify characteristics of granulomatosis with polyangiitis (GPA) associated with induction failure, describe salvage therapies and their efficacy., Methods: We conducted a nationwide retrospective case-control study of GPA with induction failure between 2006 and 2021. Each patient with induction failure was randomly paired to three controls matched for age, sex and induction treatment., Results: We included 51 patients with GPA and induction failure (29 men and 22 women). At induction therapy, median age was 49 years. Twenty-seven patients received intravenous cyclophosphamide (ivCYC) and 24 rituximab (RTX) as induction therapy. Patients with ivCYC induction failure more frequently had PR3-ANCA (93% vs 70%, P = 0.02), relapsing disease (41% vs 7%, P < 0.001) and orbital mass (15% vs 0%, P < 0.01) compared with controls. Patients with disease progression despite RTX induction therapy more frequently had renal involvement (67% vs 25%, P = 0.02) with renal failure (serum creatinine >100 µmol/l in 42% vs 8%, P = 0.02) compared with controls. After salvage therapy, remission was achieved at 6 months in 35 (69%) patients. The most frequent salvage therapy was switching from ivCYC to RTX (or vice versa), showing an efficacy in 21/29 (72%). Remission was achieved in nine (50%) patients with inappropriate response to ivCYC, while in patients with progression after RTX induction, remission was achieved in four (100%) who received ivCYC (with or without immunomodulatory therapy), but only in three (50%) after adding immunomodulatory therapy alone., Conclusion: In patients with induction failure, characteristics of GPA, salvage therapies and their efficacy vary according to induction therapy and failure modality., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pharmaceuticals such as salicylic acid are commonly detected in wastewater and surface waters, increasing concern for possible harmful effects on humans and the environment. Their difficult removal via conventional treatments raised the need for improved strategies, among which the development of bioderived adsorbents gained interest because of their sustainability and circularity. In this work, biobased cross-linked adsorbents, synthesized via a sustainable approach from starch derivatives, namely beta-cyclodextrins and maltodextrins, were at first characterized via FTIR-ATR, TGA, SEM, and elemental analysis, showing hydrophilic granular morphologies endowed with specific interaction sites and thermal stabilities higher than 300 °C. Subsequently, adsorption tests were carried out, aiming to assess the capabilities of such polymers on the removal of salicylic acid, as a case study, from water. Batch tests showed rapid kinetics of adsorption with a removal of salicylic acid higher than 90% and a maximum adsorption capacity of 17 mg/g. Accordingly, continuous fixed bed adsorption tests confirmed the good interaction between the polymers and salicylic acid, while the recycling of the adsorbents was successfully performed up to four cycles of use.

Objective: To assess how and to what extent socioeconomic status and ethnicity/race of participants are reported in randomized controlled trials (RCTs) on systemic sclerosis (SSc), and to estimate the representativeness of different ethnic/racial groups in SSc RCTs., Methods: We searched all published RCTs on SSc indexed in PubMed. We retrieved information on main features of RCTs published from 2000 onward and recorded for each study whether race/ethnicity was reported; how ethnicity/race was defined and assigned; and the number of patients included for each racial/ethnic group. Multivariable logistic regression was used to identify factors associated with race/ethnicity reporting. Proportion of races/ethnicities included in US-based RCTs on SSc was examined and compared with US demographic data., Results: We included 106 studies, mostly conducted in Europe (42%) or North America (25%), published after 2010 (74%), and enrolling a total of 6,693 patients. About one-third of studies provided information about race/ethnicity, with no improved reporting over time. Only 2 papers reported patient's socioeconomic status. Study location (US or intercontinental) was the only significant factor associated with a better reporting of race/ethnicity in multivariable analysis. In studies where race/ethnicity was reported, White patients were mostly represented (79%), followed by Asian (7%), and African American (6%). In the sensitivity analysis limited to studies from the US, underrepresentation of African American patients was observed in the 2000-2010 time period, but not later., Conclusion: Documentation of race/ethnicity and socioeconomic status is poor in RCTs on SSc. More effort should be made to document race/ethnicity and socioeconomic status and to promote diversity in SSc RCTs., (© 2022 American College of Rheumatology.)

Objective: To assess the time from completion to publication of randomized controlled trials (RCTs) on connective tissue diseases (CTDs), investigate the factors associated with, and explore the influence of significance of study results on time to publication (time-lag publication bias)., Methods: We included interventional, phase 2/3, 3, or 4 RCTs on CTDs registered in Clinicaltrials.gov from 2000 to 2016, whose results had been published in a peer-review journal less than 5 years after their completion. Main trial features, including the significance of primary outcome results, were collected. Time to publication was the time from study completion to the earliest publication date. Multivariable linear regression was used to identify factors associated with time to publication., Results: We included 62 studies, mostly phase 3 (61%) trials on pharmacologic treatments (94%); we recruited patients with systemic lupus (55%) or systemic sclerosis (23%) and planned to enroll a median of 131 (IQR [interquartile range]: 61-288) patients. Twenty-two (35%) reported at least a statistically significant primary outcome. Median time to publication was 28 months (IQR: 17-36). In a multivariable analysis, time to publication progressively improved over time (faster publication in recent years, with the average time to publication decreasing by 1.3 [95% CI: 0.3-2.3] months per year) and was not influenced by the significance of primary outcome results, funder, impact factor of the journal, number of recruiting countries, and comparator., Conclusion: A high proportion of CTDs-RCTs is published beyond 2 years from completion. We did not find evidence of time-lag publication bias, and time to publication improved over time., (© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Aims of the Study: To assess current practices in diagnosing, treating, and following-up giant-cell arteritis by specialists in Switzerland and to identify the main barriers to using diagnostic tools., Methods: We performed a national survey of specialists potentially caring for patients with giant-cell arteritis. The survey was sent by email to all members of the Swiss Societies of Rheumatology and for Allergy and Immunology. A reminder was sent to nonresponders after 4 and 12 weeks. Its questions covered the following dimensions: respondents' main characteristics, diagnosis, treatment, and imaging's role during follow-up. The main study results were summarized using descriptive statistics., Results: Ninety-one specialists, primarily aged 46-65 years (n = 53/89; 59%), working in academic or nonacademic hospitals or private practice, and treating a median of 7.5 (interquartile range [IQR]: 3-12) patients with giant-cell arteritis per year participated in this survey. Ultrasound of temporal arteries/large vessels (n = 75/90; 83%) and positron-emission-tomography-computed tomography (n = 52/91; 57%) or magnetic resonance imaging (n = 46/90; 51%) of the aorta/extracranial arteries were the most common techniques used to diagnose giant-cell arteritis with cranial or large vessel involvement, respectively. Most participants reported a short time to obtain imaging tests or arterial biopsy. The glucocorticoid tapering scheme, glucocorticoid-sparing agent, and glucocorticoid-sparing treatment duration varied among the participants. Most physicians did not follow a predefined repeat imaging scheme for follow-up and mainly relied on structural changes (vascular thickening, stenosis, or dilatation) to drive treatment choice., Conclusions: This survey indicates that imaging and temporal biopsy are rapidly accessible for diagnosing giant-cell arteritis in Switzerland but highlights heterogeneous practice in many disease management areas.

Objectives: To estimate the prevalence of long-term exposure to glucocorticoids (GCs) and to identify factors associated with, and variations in prescribing practices over time and across recruiting countries., Methods: We included patients with SSc having a visit recorded in the EUSTAR database from January 2013 onward. We analysed the prevalence and the main features of GCs users, their exposure to GCs over time, and their GCs dosages. Multivariable linear regression was used to analyse the factors identified as associated with GCs intake duration. Time trends, and variations in GCs utilization across recruiting countries were explored. Missing data were imputed using multiple imputation with chained equations., Results: The 9819 patients included were mostly females (85%), the majority had lcSSc (73%), and the median age was 58 years. At baseline, 34% of patients (n = 2769/8109) (48% dcSSc vs 29% lcSSc) were on GCs, and the median dose was 7.5 mg/day. GCs users were more frequently males and anti-Scl70 positive, and more commonly had dcSSc and more severe disease. On average, GCs users spent 25% of their follow-up time (median 33.2 months) on GCs, with no significant between-subsets difference. Notably, 33% (n = 971/2959) and 22% (n = 647/2959) of patients followed up for >1 year had received GCs for >6 and >12 months, respectively. Multivariable analysis showed that patient and disease characteristics poorly explained the variability in GCs exposure (adjusted-R2 = 0.06, P < 0.001). GCs utilization varied within and across countries, and gradually decreased over time (36% in 2013 vs 23% in 2018)., Conclusions: GCs are widely and long-term prescribed in SSc, with significant between-countries and within-country differences. A gradual decrease in their utilization has been observed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To assess the proportion, the reasons, and the factors associated with the discontinuation or nonpublication of randomized controlled trials (RCTs) on connective tissue diseases (CTDs)., Methods: We searched all interventional RCTs on CTDs registered in ClinicalTrials.gov since 2000. Two reviewers selected studies according to prespecified eligibility criteria. Completion status, publication status, and reported reasons for discontinuation or nonpublication were retrieved on ClinicalTrials.gov, through literature search, and by contacting investigators. Multivariable logistic regression was used to identify factors associated with study noncompletion and nonpublication., Results: We included 175 studies, mostly phase III, placebo-controlled trials on pharmacologic treatments recruiting patients with systemic lupus erythematosus (51%), systemic sclerosis (20%), Sjögren's syndrome (12%), or other CTDs. Fifty-eight (33%) had been discontinued, mainly for insufficient patient accrual, with no differences in discontinuation rates across the CTDs (P > 0.5). Forty-six (35%) of 130 studies having included at least 1 patient were unpublished, and 86 (65%) were published in a peer-reviewed journal after a median of 24 months (interquartile range 15-41) from completion, with a significantly higher publication rate in completed versus discontinued studies (81% versus 22%; P < 0.001). We were able to obtain reasons for nonpublication in one-third of cases. Small sample size (<100 participants) was the only factor associated with study noncompletion and nonpublication., Conclusion: One of 3 registered RCTs on CTDs fails to be completed or published. This represents a waste of resources and raises ethical concerns regarding hidden clinical data and unfruitful participation by patients., (© 2022 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

This review of the literature highlights the results of the recent randomized controlled trials about the management of systemic sclerosis (SSc) and its complications. The latest randomized studies have failed to demonstrate the utility against placebo of the injections of botulinum toxin A to achieve a better control of Raynaud's phenomenon and the efficacy of the adipose-derived cell transplantation for the treatment of hand dysfunction. Rituximab allows a significant improvement of cutaneous induration. The injections of mesenchymal stromal cells are well tolerated and should encourage future randomized trials to evaluate their efficacy. Finally, nintedanib and tocilizumab allow a reduction in the rate of decline of lung function, as well as a possible stabilization with tocilizumab., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

In rheumatology, this year has seen an expansion of knowledge about the treatment of rheumatoid arthritis, with the availability of results from randomized trials evaluating a new molecule targeting IL-6, and regarding the safety profile of tofacitinib compared to TNF-alpha inhibitors. Interesting data on the outcome of pregnancy in patients with spondylarthritis have also been published. New molecules and different treatment strategies have shown promising results in psoriatic arthritis and systemic lupus erythematosus. The utility of botulinum toxin A injections for Raynaud's phenomenon and the efficacy of transplantation of autologous adipose-derived regenerative cells for the treatment of hand dysfunctions have been questioned by 2 randomized controlled trials of patients with systemic sclerosis., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Recent guidelines for SLE recommend using a hydroxychloroquine (HCQ) dose less than 5.0 mg/kg/day to reduce the risk of retinopathy. To determine if this dose reduction would have an impact on the clinical course of SLE, we compared flare incidence in a cohort of patients with SLE treated with two different oral HCQ dosages (≤5 mg/kg/day or >5 mg/kg/day). As a secondary analysis, we compared HCQ blood levels between the two different oral dosages, and evaluated the frequency of non-adherence in patients with SLE treated with HCQ., Methods: We identified a cohort of patients with SLE taking HCQ for at least 6 months and followed for 24 months. At study entry and 6 months later, a blood venous sample was taken to measure HCQ blood levels by liquid chromatography. Incidence of new SLE flares after recruitment was put in relation to daily HCQ dose and mean HCQ blood levels. Cox regression analysis served to identify factors associated with SLE flares., Results: 83 patients were enrolled. We observed 11 (16%) flares that developed in mean 14.8 months of follow-up. The difference in terms of flare rate and mean HCQ blood levels between the two oral dosages was not statistically significant. There was a trend (p=0.08) for high HCQ dose being associated with a lower flare rate. At Cox analysis, higher HCQ blood levels and older age at baseline were protective against flare occurrence, while concomitant immunosuppressant therapy showed significant positive association. HCQ blood levels did not correlate with prescribed HCQ dose., Conclusion: Patients with low oral HCQ dosage tend to have more flares, although the difference was not statistically significant. Higher HCQ blood levels were protective against flare occurrence. The risks and benefits must be balanced in choosing HCQ dose., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Results of randomized clinical trials have demonstrated rituximab's noninferiority to cyclophosphamide as induction therapy for antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), with neither treatment having a specific advantage for granulomatosis with polyangiitis (GPA). However, post hoc analysis results have suggested that rituximab might be more effective than cyclophosphamide in inducing remission in patients with proteinase 3-positive AAV., Objective: To compare the effectiveness of rituximab and cyclophosphamide in inducing GPA remission in a large population of unselected patients., Design, Setting, and Participants: This comparative effectiveness study used multicenter target trial emulation observational data from 32 French hospitals in the French Vasculitis Study Group Registry. Groups were determined according to treatments received, without any intervention from the investigators. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Participants included patients with newly diagnosed or relapsing GPA who satisfied American College of Rheumatology classification criteria and/or Chapel Hill Consensus Conference nomenclature. Data were analyzed from October 1, 2021, to May 31, 2022., Exposures: At least 1 infusion of rituximab or cyclophosphamide for induction therapy between April 1, 2008, and April 1, 2018., Main Outcomes and Measures: The primary outcome was remission rate at month 6 (±2 months), with remission defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and prednisone dose of 10 mg/d or less. The BVAS is a validated tool for small-vessel vasculitis and used to assess the level of disease activity, with a numerical weight attached to each involved organ system. The BVAS has a range of 0 to 63 points; a score of 0 indicates no disease activity. Subgroup analyses included the primary outcome for patients with a new diagnosis, for most recently treated patients, and for patients with myeloperoxidase-ANCA positivity., Results: Among 194 patients with GPA included in the analysis (mean [SD] age, 54 [15] years; 110 men [56.7%]), 165 (85.1%) had a new diagnosis, and 147 of 182 with data available (80.8%) had proteinase 3-ANCA positivity. Sixty-one patients received rituximab and 133 received cyclophosphamide for induction therapy. In the weighted analysis, the primary outcome was reached for 73.1% of patients receiving rituximab vs 40.1% receiving cyclophosphamide (relative risk [RR], 1.82 [95% CI, 1.22-2.73]; risk difference, 33.0% [95% CI, 12.2%-53.8%]; E value for RR, 3.05). Similar results were observed in the subgroup of patients with newly diagnosed GPA and those with a more recent treatment. In the subset of 27 patients with myeloperoxidase-ANCA-positive GPA, 8 of 10 rituximab recipients and 8 of 17 cyclophosphamide recipients met the primary end point (unweighted RR, 1.73 [95% CI, 0.96-3.11])., Conclusions and Relevance: In this comparativeness effectiveness study using clinical data, rituximab induction therapy for GPA was more frequently associated with remission than cyclophosphamide. These results inform clinical decision-making concerning the choice of remission induction therapy for this subset of patients with AAV.

Background: JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers., Methods: In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk., Results: We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA., Conclusion: The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i., Competing Interests: Competing interests: KL reports personal fees from Gilead-Galapagos, Pfizer, Viatris, Celltrion, outside the submitted work. ML reports speaking fee from Boehringer Inghelheim, outside the submitted work. DM has nothing to disclose. SAB report grants from Pfizer, outside the submitted work. DC report grants, personal fees and non-financial support from Abbvie, grants, personal fees and non-financial support from Amgen, grants, personal fees and non-financial support from BMS, grants, personal fees and non-financial support from Eli Lilly, grants, personal fees and non-financial support from Merck, grants, personal fees and non-financial support from Novartis, grants, personal fees and non-financial support from Pfizer, grants, personal fees and non-financial support from Roche, grants, personal fees and non-financial support from Sanofi-Genzyme, grants, personal fees and non-financial support from UCB, grants, personal fees and non-financial support from Sandoz, outside the submitted work. CC reports personal fees from Abbvie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer outside the submitted work. RC has nothing to disclose. DDC has nothing to disclose. LD reports institutional grant from BMS outside the present work and speakers bureau from Eli Lilly and Galderma. OE has nothing to disclose. E-MH reports personal fees from AbbVie, Sanofi, Sobi ; institutional grants from Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Roche, Novartis, AbbVie outside the submitted work. DH has nothing to discloseKLH reports honoraria from Abbvie and grants from Pfizer and BMS outside the submitted work, and is supported by the NIHR Manchester Biomedical Research Centre. FI reports speaking fees from Abbvie, BMS, Eli-Lilly, Roche, MSD, Galapagos, Pfizer, Celltrion, Janssen outside the submitted work. NI reports grants from Roche, Pfizer, personal fees from AbbVie, Roche, Pfizer, UCB, Novartis,Amgen, Lilly, MSD. LK-F has nothing to disclose. EKK has nothing to disclose. TKK reports fees for speaking and/or consulting last 2 years from AbbVie, Amgen, Celltrion, Egis, Evapharma, Ewopharma, Gilead, Hikma, Janssen, Mylan, Novartis, Oktal, Pfizer, Sandoz, UCB. BFL reports personal fees from Abbvie, personal fees from Biogen, personal fees from Celgene, personal fees from Eli Lilly, personal fees from MSD, personal fees from Pfizer, personal fees from Roche, and personal fees from Novartis and Sandoz. GL reports personal fees from Abbvie, personal fees from Eli Lilly, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, personal fees from Roche, personal fees from Janssen, personal fees from BMS, outside the submitted work. DCN reports grants from Roche, during the conduct of the study; personal fees from Abbvie, personal fees from BMS, grants from Celgene, personal fees from Lilly, grant from MSD, personal fees from Novartis, personal fees from Pfizer, personal fees from UCB, outside the submitted work. KP has received honoraria for lectures and consultations from: AbbVie, BMS, Egis, Roche, Amgen, MSD, Medac, Eli Lilly, Pfizer. MPS reports personal fees from Janssen, MSD, Sanofi, outside the submitted work. ZR honoraria for lectures and consultations from: Abbvie, Pfizer, MSD, Medis, Roche, outside the submitted work. MJS reports personal fees from AbbVie, personal fees from Pfizer, personal fees from Novartis, personal fees from Roche, outside the submitted work. AS reports speaker honoraria from AbbVie, BMS, MSD, Pfizer, and Roche. PV reports speakers bureau for Eli Lilly, MSD, Galapagos, Roularta, consultancy fees from Galapagos, Gilead, Pfizer, Sanofi, Sidekick Health, Eli Lilly, Nordic Pharma, ABBVIE, Celltrion, BMS, UCB and is the grant holder from the Pfizer Chair Management of Early Rheumatoid Arthritis at KU Leuven. DSC has nothing to disclose. AF reports grants from AbbVie, BMS, Eli-Lilly, Galapagos and Pfizer and speaker honoraria (educational events or symposia) from companies producing several of the targeted therapies that are included in this analysis (honoraria < 10’000 USD): AbbVie, BMS, Eli-Lilly, Gilead, MSD, Pfizer. Clinical work in Czech Republic was partially supported by the project from the Ministry of Health for conceptual development of research organisation MZ00023728023728 (Institute of Rheumatology). BIOBADASER has received funding from Fundacion Española de Reumatología, the Spanish Medicines and Health Products Agency (Agencia Española del Medicamento y Productos Sanitarios) and equal grants from pharmaceutical companies (AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Regeneron, Roche, Samsung, Schering‐Plough and UCB). BioRx.si has received funding for clinical research paid to Društvo za razvoj revmatologije from AbbVie, Roche, Medis, MSD, Biogen, Amgen, Sanofi, Celgene and Pfizer. The British Society for Rheumatology Biologics Register in Rheumatoid Arthritis (BSRBR-RA) is funded by a grant from the British Society for Rheumatology (BSR). The BSR currently receives funding from Abbvie, Amgen, Celltrion HC, Eli Lilly, Pfizer, Samsung Bioepis, Sanofi, Sandoz and in the past Hospira, MSD, Roche, SOBI and UCB. This income finances a wholly separate contract between the BSR and The University of Manchester to host the BSRBR-RA. All decisions concerning study design, data capture, analyses, interpretation and publication are made autonomously of any industrial contribution. The BSRBR-RA would like to gratefully acknowledge the support of the National Institute for Health Research, through the Local Clinical Research Networks in England (and equivalent organisations in the devolved nations) at participating centres and the BSRBR-RA Control Centre Consortium. DANBIO was partially supported by public and private funding (AbbVie, Biogen, Bristol Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB). NOR-DMARD was has been supported with research funding to Diakonhjemmet Hospital from AbbVie, Amgen, BMS, MSD, Novartis, Pfizer and UCB. The RABBIT register is currently supported by an unconditional grant with equal parts from AbbVie, Amgen, BMS, Celltrion, Fresenius Kabi, Galapagos, Hexal, Lilly, MSD, Viatris, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB. REUMA. PT is supported by unrestricted grants from Abbvie, Biogen, Celgene, MSD, Roche, Sanofi and Pfizer. ROB-FIN is funded by AbbVie, Hospira, BMS, MSD, Pfizer, Roche and UCB. The Romanian Registry of Rheumatic Diseases (RRBR) uses unrestricted grants from AbbVie, Pfizer, Eli Lilly, Ewopharma, Nopvartis MSD, Roche, UCB, and BMS. Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) database is sponsored by public and industrial support (http://scqm.ch/en/sponsoren/)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To describe the main features at diagnosis and evolution over time of patients with localized granulomatosis with polyangiitis (L-GPA) compared with those of systemic GPA (S-GPA)., Methods: EULAR definitions of L-GPA, i.e. upper and/or lower respiratory tract involvement, and S-GPA were applied to patients from the French Vasculitis Study Group Registry. L-GPA and S-GPA patients' characteristics at diagnosis and long-term outcomes were analysed and compared., Results: Among the 795 Registry patients, 79 (10%) had L-GPA. Their main clinical manifestations were rhinitis, lung nodules, sinusitis and otitis. L-GPA vs S-GPA patients at diagnosis, respectively, were younger, more frequently had saddle nose deformity or subglottic stenosis and were less often PR3-ANCA-positive. L-GPA vs S-GPA induction therapy less frequently included CYC but more often a combination of MTX and glucocorticoids; 64% of MTX-treated patients experienced disease progression within 18 months post-diagnosis. L- and S-GPA patients' estimated relapse-free-survival probabilities, relapse rates and refractory disease rates at each time point were comparable, but L-GPA patients had more frequent ENT and lung relapses, and higher overall survival rates (P<0.02). Over a median follow-up of 3.5 years, 18 (22.8%) L-GPA progressed to S-GPA, either as a relapse after a period in remission or more frequently in the context of refractory disease. L-GPA patients experienced more ENT-related damage., Conclusions: The relapse risks of L-GPA and S-GPA were similar, but relapse patterns differed and L-GPA overall survival rate was higher. About one-quarter of L-GPA patients developed S-GPA over time, but without end-stage organ involvement., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To describe disease presentation and long-term outcome of granulomatosis with polyangiitis (GPA) patients according to blood eosinophils count (Eos) at vasculitis diagnosis., Methods: Data from newly diagnosed GPA patients registered in the French Vasculitis Study Group database with available eosinophil count at diagnosis were reviewed. Disease characteristics, rate and type of relapses, and overall survival were analysed according to Eos, categorized as normal (<500/mm3), mild-to-moderate hypereosinophilia (HE) (between 500 and 1500/mm3) and severe HE (>1500/mm3)., Results: Three hundred and fifty-four patients were included. At diagnosis, 90 (25.4%) patients had HE ≥500/mm3; they were more likely male (73% vs 56%, P = 0.006) and had more frequent cutaneous manifestations (49% vs 33%, P = 0.01), peripheral neuropathy (32% vs 17%, P = 0.004) and higher BVAS (21 vs 18, P = 0.01), compared with those with Eos <500/mm3. Patients with severe HE (n = 28; median Eos 2355, range 1500-9114) had more frequent renal function worsening at presentation (P = 0.008). After a median follow-up of 3.95 (interquartile range 1.95-6.76) years, no difference was found in overall relapse rates according to baseline Eos, but those with HE experienced more neurological (P = 0.013) and skin (P = 0.024) relapses and had more frequently peripheral neuropathy as damage at last follow-up (P = 0.02). Overall survival was not significantly different in patients with normal Eos or HE at diagnosis. (P = 0.08)., Conclusions: Blood HE at diagnosis, observed in about one-quarter of GPA patients, identifies a subgroup of patients with a more severe disease and higher rate of skin and neurological involvement both at presentation and during follow-up., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To investigate whether antineutrophil cytoplasm antibody (ANCA)-negative and myeloperoxidase (MPO)-ANCA-positive granulomatosis with polyangiitis (GPA) differ from proteinase-3 (PR3)-ANCA-positive GPA., Methods: Diagnostic characteristics and outcomes of newly diagnosed French Vasculitis Study Group Registry patients with ANCA-negative, MPO-ANCA-positive or PR3-ANCA-positive GPA satisfying American College of Rheumatology criteria and/or Chapel Hill Conference Consensus Nomenclature were compared., Results: Among 727 GPA, 62 (8.5%) were ANCA-negative, 119 (16.4%) MPO-ANCA-positive and 546 (75.1%) PR3-ANCA-positive. ANCA-negative patients had significantly (p<0.05) more limited disease (17.7% vs 5.8%) and less kidney involvement (35.5% vs 58.9%) than those PR3-ANCA-positive or MPO-ANCA-positive, with comparable relapse-free (RFS) and overall survival (OS). MPO-ANCA-positive versus PR3-ANCA-positive and ANCA-negative patients were significantly more often female (52.9% vs 42.1%), older (59.8 vs 51.9 years), with more frequent kidney involvement (65.5% vs 55.2%) and less arthralgias (34.5% vs 55.1%), purpura (8.4% vs 17.1%) or eye involvement (18.5% vs 28.4%); RFS was similar but OS was lower before age adjustment. PR3-positive patients' RFS was significantly lower than for ANCA-negative and MPO-positive groups combined, with OS higher before age adjustment. PR3-ANCA-positivity independently predicted relapse for all GPA forms combined but not when comparing only PR3-ANCA-positive versus MPO-ANCA-positive patients., Conclusions: Based on this large cohort, ANCA-negative versus ANCA-positive patients more frequently had limited disease but similar RFS and OS. MPO-ANCA-positive patients had similar RFS but lower OS due to their older age. PR3-ANCA-positive GPA patients' RFS was lower than those of the two other subsets combined but that difference did not persist when comparing only PR3 versus MPO-ANCA-positive patients., Competing Interests: Competing interests: Individual sources of potential conflict are as follows. XP: speaking fees and honoraria: Boehringer Ingelheim, Sanofi; Congress inscription/travel/accommodations: Sanofi. CP: consultancies, speaking fees and honoraria: Hoffman-La Roche, Sanofi, Chemocentryx, InflaRx GmbH, GSK, AstraZeneca. AK: consultancies, speaking fees and congress inscription/travel/accommodations: Roche, AstraZeneca, Vifor. TQ: congress inscription/travel/accommodations: MSD, Sanofi-Genzyme, LFB. BT: consultancies, speaking fees and honoraria: Roche, Grifols, LFB, AstraZeneca. LM: consultancies, speaking fees and honoraria: Roche. All authors have been coinvestigators in academic studies for which rituximab was provided by Roche Pharma., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with SLE have an endothelial dysfunction (ED), which is considered the earliest marker of cardiovascular (CV) disease. Endothelial cell activation induced by proinflammatory cytokines is defined by the endothelial expression of cell-surface adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin. The aim of this study was to investigate whether serum endothelial adhesion molecule levels are influenced by blood hydroxychloroquine (HCQ) levels in SLE., Methods: Consecutive patients with SLE taking a stable dose of HCQ were investigated. At study entry and 6 months later HCQ blood levels were quantified by tandem mass spectrometry. Serum levels of P-selectin, E-selectin, ICAM-1 and VCAM-1 were also measured using a Luminex 200 instrument. Comparison of endothelial soluble adhesion molecules in groups with different HCQ blood levels was performed by t-test., Results: 83 patients with SLE were enrolled. Correlation were demonstrated between mean blood HCQ concentrations and endothelial soluble adhesion molecules (E-selectin, ICAM-1 and VCAM-1). Moreover, serum levels of ICAM-1 and VCAM-1 were significantly lower in the patients with SLE with HCQ blood levels >500 ng/mL (83.67±52.8 ng/mL vs 158.81±125.1 ng/mL and 8.9±2.2 ng/mL vs 10.4±2.3 ng/mL). Serum levels of E-selectin were nearly significantly lower in the patients with SLE with HCQ blood levels >500 ng/mL (64.7±30.2 ng/mL vs 71.6±42.2 ng/mL, p=0.06). No significant difference in concentration of P-selectin was detected., Conclusions: In the present study, there was a trend towards higher adhesion molecules levels with lower HCQ blood levels in patients with SLE. Further longitudinal studies will determine whether changes in endothelial biomarkers reflect decreased clinical CV events., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To estimate the extent of and the reasons for ineligibility in randomized controlled trials (RCTs) of SSc patients included in the EUSTAR database, and to determine the association between patient's features and generalizability of study results., Methods: We searched Clinicaltrials.gov for all records on interventional SSc-RCTs registered from January 2013 to January 2018. Two reviewers selected studies, and information on the main trial features were retrieved. Data from 8046 patients having a visit in the EUSTAR database since 2013 were used to check patient's eligibility. The proportion of potentially eligible patients per trial, and the risk factors for ineligibility were analysed. Complete-, worst- and best-case analyses were performed., Results: Of the 37 RCTs included, 43% were conducted in Europe, 35% were industry-funded, and 87% investigated pharmacological treatments. Ninety-one percent of 8046 patients included could have participated in at least one RCT. In complete-case analysis, the median [range] proportion of eligible patients having the main organ complication targeted by each study was 60% [10-100] in the overall sample of trials, ranging from 50% [32-79] for trials on skin fibrosis to 90% [34-77] for those targeting RP. Among the criteria checked, treatment- and safety-related but not demographic were the main barriers to patient's recruitment. Older age, absence of RP, and lower mRSS were independently associated with the failure to fulfill criteria for any of the included studies., Conclusions: Patient's representativeness in SSc-RCTs is highly variable and is driven more by treatment- and safety-related rather than demographic criteria., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In rheumatology, this year has seen an expansion of knowledge about the effects of COVID and the vaccine response in patients with autoimmune diseases, but also a re-examination of the usual doses of glucocorticoids in vasculitides and new treatments strategies for diseases such as systemic lupus erythematosus, spondylarthritis and rheumatoid arthritis. New criteria for imaging assessment in spondylarthritis and new management guidelines for patients with low back pain have also been proposed., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objectives: Only a third of patients with eosinophilic granulomatosis with polyangiitis (EGPA) are ANCA-positive, mainly directed against MPO. ANCA directed against PR3 are rarely found in EGPA. We aimed to examine the significance of PR3-ANCA in EGPA., Methods: We set up a retrospective European multicentre cohort including 845 patients. Baseline characteristics and outcomes were analysed and compared according to ANCA status., Results: ANCA status was available for 734 patients: 508 (69.2%) ANCA-negative, 210 (28.6%) MPO-ANCA and 16 (2.2%) PR3-ANCA. At baseline, PR3-ANCA patients, compared with those with MPO-ANCA and ANCA-negative, less frequently had active asthma (69% vs 91% and 93%, P = 0.003, respectively) and peripheral neuropathy (31% vs 71% and 47%, P < 0.0001), more frequently had cutaneous manifestations (63% vs 38% and 34%, P = 0.03) and pulmonary nodules (25% vs 10% and 8%, P = 0.046), and lower median eosinophil count (1450 vs 5400 and 3224/mm3, P < 0.0001). Vasculitis relapse-free survival was shorter for PR3-ANCA (hazard ratio 6.05, P = 0.005) and MPO-ANCA patients (hazard ratio 1.88, P = 0.0002) compared with ANCA-negative patients., Conclusion: PR3-ANCA EGPA patients differ from those with MPO-ANCA and negative ANCA, and share clinical features with granulomatosis with polyangiitis. This suggests that PR3-ANCA EGPA could be a particular form of PR3-ANCA-associated vasculitis., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Characteristics of Swiss patients with systemic sclerosis have not been described so far. The aim of the current study was to identify unmet needs in comparison with other European countries that could inform specific interventions to improve the care of systemic sclerosis patients., Methods: We analysed Swiss and other European systemic sclerosis patients registered in European Scleroderma Trials And Research (EUSTAR) and the Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) cohort. Demographics, clinical profiles, organ involvement and survival of established, early/mild and very early / very mild systemic sclerosis patients were described and compared between the cohorts., Results: We included 679 Swiss and 8793 European systemic sclerosis patients in the analysis. Over 95% of patients in both cohorts were Caucasian, disease subsets were similar, and no age difference was found. The Swiss cohort had more male patients (25% vs 16% European, p = 0.005) and higher prevalence of early/mild and very early / very mild patients (26.1 vs 8.5% European and 14.9% vs 6.7% European, respectively, both p &lt;0.0001). Disease duration in established systemic sclerosis patients at first presentation was numerically shorter but not significant in the Swiss cohort: 5.0 years (1&ndash;12) Swiss vs 6.0 years (2&ndash;12) years European, p = 0.055). Despite the earlier referral of Swiss patients to systemic sclerosis expert centres, they showed evidence of more severe disease, particularly in the limited cutaneous systemic sclerosis subset, but no differences in overall survival on longitudinal follow-up were observed., Conclusion: This is the first report of the national Swiss EUSTAR cohort. It identifies earlier referral to systemic sclerosis expert centres, before major organ damage occurs, and when outcome can still be modified, as a priority to improve care of patients with systemic sclerosis.

Objective: To describe the characteristics and long-term outcomes of patients with granulomatosis with polyangiitis (GPA) from the French Vasculitis Study Group database., Methods: Patients' clinical and laboratory characteristics, Birmingham Vasculitis Activity Score (BVAS)-assessed disease activity, malignancies, opportunistic infections, and vital status were collected at diagnosis and each visit. Estimated probabilities and predictors of overall (OS) and relapse-free survival (RFS) were analyzed by Cox regression., Results: We enrolled 795 newly diagnosed patients, followed for a median of 3.5 years. Initial clinical manifestations involved ear, nose & throat (ENT; 80%), lungs (68%) and kidneys (56%). Among the 728 available ELISA results, 75.0% were PR3-ANCA-positive, 16.5% MPO-ANCA-positive and 62 (8.5%) ANCA-negative. Relapses occurred in 394 (50%) patients, involving ≥1 organ(s) affected at onset in 179 (46%), mainly ENT, lungs and kidneys, with mean BVAS 10.2 points below that at diagnosis (p<0.001). Five- and 10-year RFS rates were 37% and 17%, respectively. PR3-ANCA-positivity independently predicted relapse (p = 0.05) and prolonged survival (p = 0.038). OS-but not RFS-improved significantly over time (p<0.001); 10-year OS reached 88.2% (95% CI 83.9 to 92.7) for the 660 patients diagnosed after 2000. Infections were the main causes of death. Malignancy or opportunistic infection each occurred in ≤5% of the patients., Conclusion: Survival has improved dramatically over the last decades but the high relapse rate remains a major concern for GPA patients, once again stressing the need for therapeutic strategy optimization to lower it. PR3-ANCA-positivity was associated with increased probability of relapse and survival., Competing Interests: Declaration of Competing Interests CP has declared consultancies, speaking fees and honoraria (Hoffman-La Roche, Sanofi, Chemocentryx, InflaRx GmbH and GSK <$10,000). TQ has declared receiving fees for congress inscriptions/travel/accommodations (MSD, Sanofi-Genzyme, LFB <$5000). BT has declared consultancies, speaking fees and honoraria (Roche, Grifols, LFB, AstraZeneca <$10,000). LM has declared consultancies, speaking fees and honoraria (Roche <$10,000). XP has declared speaking fees and honoraria (Boehringer Ingelheim, Sanofi <$10,000) and for congress inscriptions/travel/accommodations (Sanofi <$5000). All authors have been coinvestigators in academic studies for which rituximab was provided by Roche Pharma. No other conflicts were reported. MI, DSC, PC, MH, AA, FL, MR, OA, BB, OD, FM, EH, AK, CK, NJ-C, J-FV, CB-D, PG, ALQ, CdM, AR, and LG have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Data on sustained remission of granulomatosis with polyangiitis (GPA) after discontinuation of therapy (referred to as GPA with sustained remission off-therapy [SROT]) are scarce. In the present study, SROT among GPA patients from the French Vasculitis Study Group Registry was evaluated to identify factors associated with its occurrence and durability., Methods: For inclusion of patients in the study, the diagnosis of GPA had to meet the GPA classification criteria defined by the American College of Rheumatology and/or the revised Chapel Hill Consensus Conference nomenclature for vasculitis. SROT was defined as achievement of remission (a Birmingham Vasculitis Activity Score of 0) that was sustained for ≥6 consecutive months after having discontinued glucocorticoid (GC) and immunosuppressant treatments. The characteristics of the patients at baseline and treatments received were compared at 3, 5, and 10 years postdiagnosis according to whether or not SROT had been reached and maintained., Results: Among 795 patients with GPA, 92 GPA patients with SROT at 3 years postdiagnosis were compared to 342 control subjects who had experienced disease relapse and/or were still receiving GCs or immunosuppressants. No baseline differences were found, but patients with SROT at 3 years postdiagnosis had more frequently received intravenous cyclophosphamide as induction therapy compared to control subjects (P = 0.01), with a higher median number of infusions (P = 0.05). At 5 years postdiagnosis, no baseline differences were observed between groups, but patients with SROT at 5 years postdiagnosis had received more cyclophosphamide infusions compared to control subjects (P = 0.03). More patients with SROT had received rituximab as maintenance therapy than control subjects at 3 years and 5 years postdiagnosis (P = 0.09 and P < 0.001, respectively). Of the 74 patients enrolled in the GPA Registry with 10-year follow-up data after having received conventional maintenance therapy, 15 (20%) had reached SROT at 3 years, and 5 (7%) maintained SROT at 10 years postdiagnosis., Conclusion: After conventional therapies, 7% of GPA patients had reached SROT at 10 years postdiagnosis. No baseline vasculitis characteristics distinguished patients who achieved/maintained SROT from those who experienced disease relapse and/or those who continued to receive GCs or immunosuppressant therapy, but patients with SROT had received more intensive induction therapy and rituximab as maintenance therapy more frequently., (© 2020, American College of Rheumatology.)

This article synthesizes the main aspects of the management of systemic lupus erythematosus patients in the context of the COVID-19 pandemic based on published literature. We will therefore develop on topics such as the risk of getting infected, the differences in COVID-19 clinical course and severity compared to general population, the role of antiphospholipid antibodies in thrombotic complications, and treatment strategies., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: The analysis of the main features of randomized controlled trials (RCTs) on ANCA-associated vasculitis (AAV) can inform future study design., Methods: We searched within the International Clinical Trials Registry Platform all registered RCTs on AAV from October 2008 to December 2018. Two reviewers selected studies according to pre-specified eligibility criteria. We retrieved information including countries, funding, design, sample sizes, eligibility criteria, primary outcomes (POs), and treatments., Results: Among the 40 RCTs identified, 22 (55%) were conducted in Europe, 29 (72,5%) in a single country, 14 (35%) were industry-funded. The median number of patients planned to enrol was 68 (IQR 36-138). Only 28% of RCTs targeted a single vasculitis, and ANCA negative patients were not included in about 40% of studies. Interventions investigated were mainly drugs given to induce (40%) or maintain (32.5%) remission. Eighty-five percent of POs were considered being 'patient-important', but discrepancies in definition of disease states, such as remission or relapse were observed. Glucocorticoids use was part of the PO in < 25% of studies. The number of trials targeting a single disease, non-industry funded, incorporating glucocorticoids in PO, as well as the planned sample size increased over time., Conclusion: Despite the important achievements in the field, a better harmonization of eligibility, and outcome criteria across studies is an important objective to pursue in next future.

Targeted therapies are nowadays commonly used in connective tissue diseases and vasculitis. Experts recommend the use of belimumab and rituximab in refractory and/or severe cases of lupus. Rituximab can be also considered in difficult to treat cases of Sjögren's disease or myositis. Nintedanib seems a very promising weapon in the management of systemic sclerosis-associated pulmonary fibrosis. Regarding vasculitis, rituximab has become the preferred treatment for granulomatosis with polyangiitis and microscopic polyangiitis. Finally, tocilizumab is recommended as a steroid-sparing agent in giant cell arteritis. Further clinical trials are warranted to study the efficacy of other targeted therapies in connective tissue diseases and vasculitis., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objective: To provide a comprehensive overview of interventional clinical trials registered in international databases and planned and conducted within the last 10 years in patients with systemic sclerosis (SSc)., Methods: We searched the International Clinical Trials Registry Platform for all records on interventional clinical trials targeting patients with SSc performed since September 2007. Two reviewers selected studies according to the prespecified eligibility criteria. Information on start date, country of origin, funding sources, phase of development, study design, (planned) sample size, enrollment status, outcomes, disease complication, and treatments investigated were retrieved and summarized., Results: Among the 198 eligible studies identified (122 randomized controlled trials [RCTs; 62%]), 87 (30%) were conducted in Europe, 165 (83%) in a single country, and 81 (41%) were industry-funded. The majority of trials investigated pharmacologic treatments (75%), mostly nonbiotherapies (57%). RCTs were mostly 2-arm (82%) placebo-controlled (71%) studies with a median number of patients enrolled or planned to be enrolled of 40 (interquartile range 25-77 [range 10-586]). Twenty-one RCTs (17%) planned to enroll or enrolled >100 patients. Time to assess the primary outcome was found to be adequate in 29% to 50% of RCTs retrieved. Patients age >65 years were excluded in 14% of studies. SSc complications more frequently investigated in overall studies were skin thickness (26%), Raynaud's phenomenon/digital ulcers (24%), and interstitial lung disease (14%)., Conclusion: The SSc research landscape is dominated by small, short, and mainly placebo-controlled trials, especially investigating pharmacologic treatments. Some patients' needs continue to be neglected., (© 2018, American College of Rheumatology.)