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Aims: To analyse the prescription of biologics (bDMARDs) in chronic inflammatory rheumatic diseases (CIRD) from Tunisian National Health Insurance (CNAM) data and to estimate their direct costs and associated factors., Methods: One hundred and nine consecutive patients who received at least one bDMARDs during a six-month period from January to June 2022 were analysed. Clinical and therapeutic parameters as well as data related to the choice of bDMARDs were identified. Direct costs were assessed. Excess costs were considered if the monthly costs exceeded 2200 Tunisian dinars (TD) per patient., Results: The most common CIRD was axial spondylarthritis (AS) in 44% and rheumatoid arthritis (RA) in 37.6% of cases. Juvenile idiopathic arthritis represented 2.7% of cases. In Tunisia, prescribing of bDMARDs is concentrated in the coastal regions and follows the distribution of rheumatologists. Certolizumab pegol was the most prescribed agent in 45% of cases. No significant association was found between the choice of bDMARD and the characteristics of patients, CIRD or prescribers. The total monthly cost of bDMARDs was 225,535 ± 1269 TD. Overspending was significantly associated with initial high DAS28 in RA and young age and total hip replacement in AS., Conclusion: Prescription of bDMARDs in CIRD is mainly for AS and in the coastal regions of Tunisia. The burden is considerable, partly due to the high cost of biologics. Data from this study may enable public health managers to better allocate the limited resources available for patient care and to develop medico-economic strategies to reduce health care costs.

Background: Parvovirus B19 infection has been associated with various clinical entities including musculoskeletal manifestations and the development of different autoimmune diseases. The aim of our study is to examine the musculoskeletal manifestations associated with acute parvovirus B19 infection and the possible development of chronic autoimmune rheumatic diseases., Patients and Methods: Retrospective cohort study that included adult hospitalized patients diagnosed with an acute parvovirus B19 infection between 1 January 2021 and 1 February 2024. Subjects were followed-up for 6-12 months after hospitalization aiming to identify patients who developed chronic autoimmune rheumatic diseases., Results: The study included 23 patients diagnosed with acute parvovirus B19 infection. Patients were predominantly females (16, 69.6%) with mean age at diagnosis of 39.3 ± 13.11 years. Most patients were Jewish (15, 65.2%). The two most common acute symptoms were fever (82.6%) and myalgia (56.5%). Polyarthritis was present only in three patients (13%) and all of them had wrists involvement. Anti-nuclear antibodies and rheumatoid factor were the most common autoantibodies present with equal prevalence each (13%). Five patients were treated with prednisone during the acute phase (21%), two (8.7%) of them needed drug escalation and were subsequently treated with hydroxychloroquine and methotrexate. One patient developed systemic lupus erythematosus during the first 6 months of follow-up., Conclusion: Musculoskeletal manifestations developing during acute parvovirus B19 are usually self-limited with only a small minority of patients developing chronic autoimmune diseases. It is crucial to differentiate self-limited manifestations related to acute parvovirus B19 from idiopathic autoimmune diseases aiming to avoid unnecessary immunosuppressive therapy., (© 2024 The Author(s). International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background and Objectives: Biosimilars are cost-effective alternatives to reference products for patients with inflammatory bowel diseases (IBD) and chronic inflammatory rheumatic diseases (CIRD), but patient beliefs can affect adherence to the transition. This study aimed to explore patient experience and satisfaction after switching to CT-P17, a high-concentration (100 mg/mL), citrate-free adalimumab biosimilar., Patients and Methods: This observational, multicenter, prospective French study included adult patients with IBD or CIRD who switched to CT-P17 from reference adalimumab (R-ADA; 100 mg/mL) or a low-concentration adalimumab biosimilar (ADA-BioS; 50 mg/mL). Patients completed online questionnaires to assess treatment perceptions, satisfaction, and tolerance at study inclusion (under previous treatment) and over 3 months of CT-P17 treatment. The primary criterion was overall patient satisfaction, which was assessed with the question, "What is your global satisfaction with the CT-P17 injection?", using a 7-point Likert scale. Multivariate logistic regression analysis was performed to identify factors associated with increased treatment satisfaction after switching to CT-P17., Results: The total analysis population included 232 patients (IBD 72.0%, CIRD 28.0%). Median patient age was 57.0 years (interquartile range [IQR] 46.0-63.0), 50.4% were men, and median disease duration was 9 years (IQR 5-16). Approximately half of the cohort (51.2%) switched to CT-P17 from an ADA-BioS (including 19.4% from an ADA-BioS with citrate) and half (48.7%) from R-ADA. The proportion of patients who were satisfied with treatment was stable between baseline (under previous treatment) and 3 months (under CT-P17). More patients reported increased satisfaction after switching to CT-P17 from an ADA-BioS (22.7% vs 8.0% when switching from R-ADA; p = 0.002), or from an ADA-BioS containing citrate (28.9% vs 12.3% when switching from a citrate-free ADA-BioS; p = 0.008). Independent prognostic factors for increased satisfaction were previous treatment with an ADA-BioS (odds ratio [OR] 2.88 [95% confidence interval 1.17-7.08]; p = 0.021) and pain at the injection site under previous treatment (OR 1.26 [1.08-1.47]; p = 0.004). Significantly fewer patients reported pain, redness, itching, and hematoma after 3 months of CT-P17 treatment versus baseline (p < 0.001)., Conclusions: The majority of patients had stable or increased treatment satisfaction after switching from R-ADA or an ADA-BioS to CT-P17. In particular, switching to CT-P17 from a low-concentration ADA-BioS or an ADA-BioS containing citrate was associated with increased patient satisfaction. An improvement in overall tolerance with CT-P17 versus previous adalimumab treatment was also reported., Trial Registration: ClinicalTrials.gov identifier NCT05427942, registered June 22, 2022., (© 2024. The Author(s).)

Chronic rheumatological diseases are multifactorial conditions in which both the neuroendocrine hormone pathway, including cortisol, sex hormones and active vitamin D3 (calcitriol), all deriving from cholesterol, and the epigenetic modifications that they cause play an important role. In fact, epigenetics modulates the function of the DNA of immune cells, through three main mechanisms: DNA methylation, modifications to the histones that make up chromatin and production of non-coding RNAs (microRNA - miRNA). In this narrative review, the main data regarding the epigenetic modifications induced by cortisol, 17β-oestradiol, progesterone, testosterone and calcitriol on immune cells were collected, discussing how these can interfere in the predisposition and course of chronic rheumatological diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis). An ever-increasing number of miRNAs have been identified, which are produced by neuroendocrine hormones and can influence the inflammatory-fibrotic response at various levels. Concerning the involvements of the neuro-endocrine-immunology within the pathophysiology of rheumatic diseases, the epigenetic effects induced by steroid hormones must be taken into consideration to evaluate their impact on the progression of the single condition and even inside the single patient.

Anti-Interleukin-1 (Anti-IL-1) drugs are used to treat some chronic rheumatic diseases that can affect young people, including women of childbearing age. Two anti-IL-1 drugs are available in France: anakinra and canakinumab. Data on their use during pregnancy are still limited. Based on the published literature, we carried out a review of the use of these anti-IL-1 therapies during pregnancy: therapeutic indications, pharmacological profiles and assessment of embryonic, fetal and neonatal risks. Based on this analysis, and given the absence of any reported concern, it is possible to consider the use of these two treatments during pregnancy if the clinical situation so requires and under certain conditions. Based on the data available to date, anakinra should be preferred to canakinumab whenever possible., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Purpose of Review: Medical cannabis (MC) has entered mainstream medicine by a unique route. Regulatory acceptance as a medical product in many jurisdictions has bypassed the traditional evidence-based pathway required for therapies. Easier access to MC, especially related to recreational legalization of cannabis, has led to widespread use by patients for symptom relief of a variety of medical conditions and often without medical oversight. Musculoskeletal pain remains the most common reason for MC use. This review examines real-world issues pertaining to MC and offers some guidance for clinical care of patients with rheumatic diseases being treated with MC., Recent Findings: Controlled clinical studies of cannabis products in patients with rheumatic diseases have been small and tested a range of compounds, routes of administration, and clinical populations, limiting our ability to generate conclusions on MC's effectiveness in this population. Observational cohort studies and surveys suggest that use of MC and related products in patients with rheumatic diseases improves pain and associated symptoms but is commonly accompanied by mild to moderate side effects. Conflicting evidence contributes to practitioner and patient uncertainty regarding the use of MC for rheumatic disease-related pain. Despite promising preclinical and observational evidence that MC and cannabis-derived compounds are useful in the management of rheumatic disease-related pain, there remains limited high-quality clinical evidence to substantiate these findings. There are a significant number of clinical trials on this topic currently planned or underway, however, suggesting the next decade may yield more clarity. Nevertheless, given that many people with rheumatic diseases are using cannabis products, healthcare professionals must remain apprised of the evidence pertaining to cannabinoids, communicate such evidence to patients in a meaningful way that is free from personal bias and stigma, and maintain strong collaborative clinical care pertaining to MC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Drugs used to treat rheumatic disease are associated with pneumotoxicity (drug-induced lung disease), but little is known about associated risk factors., Aim: To determine expert physician-perceived risk factors for developing pneumotoxicity in patients with rheumatologic conditions., Methods: A modified international 3-tier Delphi exercise was performed. Tier 1 determined patient and drug variables that physicians perceive to be risk factors. Tier 2 determined degree of risk associated with the Tier-1 derived variables. Tier 3 aimed to internally validate and stratify exemplar cases into risk categories., Results: 134 pulmonologists and 49 rheumatologists responded to Tier 1;157 physicians completed all tiers. Perceived risk factors included: drug type; history of previous pneumotoxicity; age; smoking; underlying rheumatic disease type and activity; renal function; pulmonary hypertension; left ventricular failure;presence, nature, severity and progression of pre-existing interstitial lung disease. Tier 2 data stratified these variables into risk profiles e.g. never versus current smoking was perceived as low and high risk respectively. An example of perceived high risk resulting from Tier 3 is a 75-year-old current smoker with high-activity rheumatoid arthritis (RA) with severe, progressive ILD being started on methotrexate. A perceived low risk is a 75-year-old currentsmoker with moderate-activity RA and emphysema with no cardiac or renal disease and no pre-existing ILD being started on rituximab. A risk prediction scoring tool is being developed to be used in validation studies., Conclusion: This modified Delphi exercise defined and stratified the perceived risk factors for developing pneumotoxicity. Age, current smoking, high underlying rheumatological disease activity, HRCT definite UIP and honeycombing, severity and progression of pre-existing ILD were perceived to be the highest risk-factors., (© 2024. The Author(s).)

Artemisinin and its derivatives are widely recognized as first-line treatments for malaria worldwide. Recent studies have demonstrated that artemisinin-based antimalarial drugs, such as artesunate, dihydroartemisinin, and artemether, not only possess excellent antimalarial properties but also exhibit antitumor, antifungal, and immunomodulatory effects. Researchers globally have synthesized artemisinin derivatives like SM735, SM905, and SM934, which offer advantages such as low toxicity, high bioavailability, and potential immunosuppressive properties. These compounds induce immunosuppression by inhibiting the activation of pathogenic T cells, suppressing B cell activation and antibody production, and enhancing the differentiation of regulatory T cells. This review summarized the mechanisms by which artemisinin and its analogs modulate excessive inflammation and immune responses in rheumatic and skeletal diseases, autoimmune inflammatory diseases, and autoimmune disorders, through pathways including TNF, Toll-like receptors, IL-6, RANKL, MAPK, PI3K/AKT/mTOR, JAK/STAT, and NRF2/GPX4. Notably, in the context of the NF-κB pathway, artemisinin not only inhibits NF-κB expression by disrupting upstream cascades and/or directly binding to NF-κB but also downregulates multiple downstream genes controlled by NF-κB, including inflammatory chemokines and their receptors. These downstream targets regulate various immune cell functions, apoptosis, proliferation, signal transduction, and antioxidant responses, ultimately intervening in systemic autoimmune diseases and autoimmune responses in organs such as the kidneys, nervous system, skin, liver, and biliary system by modulating immune dysregulation and inflammatory responses. Ongoing multicenter randomized clinical trials are investigating the effects of these compounds on rheumatic, inflammatory, and autoimmune diseases, with the aim of translating promising preclinical data into clinical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Long, Xiang, Xiao, Min, Qu, Zhang and Zeng.)

Objectives: To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs)., Methods: Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors., Results: The study included 7336 patients with I-RMD, with 272 of 7336 (3.7%) experiencing flares and 121 of 7336 (1.6%) experiencing flares requiring starting a new medication or increasing the dosage of an existing medication. Factors independently associated with increased odds of flare were: female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease at the time of vaccination (low disease activity (LDA), OR=1.45, 95% CI=1.08 to 1.94; moderate/high disease activity (M/HDA), OR=1.37, 95% CI=0.97 to 1.95; vs remission), and cessation/reduction of antirheumatic medication before or after vaccination (OR=4.76, 95% CI=3.44 to 6.58); factors associated with decreased odds of flare were: higher age (OR=0.90, 95% CI=0.83 to 0.98), non-Pfizer/AstraZeneca/Moderna vaccines (OR=0.10, 95% CI=0.01 to 0.74; vs Pfizer), and exposure to methotrexate (OR=0.57, 95% CI=0.37 to 0.90), tumour necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) or rituximab (OR=0.27, 95% CI=0.11 to 0.66), versus no antirheumatic treatment. In a multivariable model using new medication or dosage increase due to flare as the dependent variable, only the following independent associations were observed: active disease (LDA, OR=1.47, 95% CI=0.94 to 2.29; M/HDA, OR=3.08, 95% CI=1.91 to 4.97; vs remission), cessation/reduction of antirheumatic medication before or after vaccination (OR=2.24, 95% CI=1.33 to 3.78), and exposure to methotrexate (OR=0.48, 95% CI=0.26 to 0.89) or rituximab (OR=0.10, 95% CI=0.01 to 0.77), versus no antirheumatic treatment., Conclusion: I-RMD flares following SARS-CoV-2 vaccination were uncommon. Factors associated with flares were identified, namely higher disease activity and cessation/reduction of antirheumatic medications before or after vaccination., Competing Interests: Competing interests: BF does not report conflicts of interest. SL-T does not report conflicts of interest. KLH reports non-personal speaker's fees from AbbVie and grant income from BMS and Pfizer, all unrelated to this manuscript; and her institute was supported by EULAR for COVAX database management. LG reports research grants from Amgen, Galapagos, Lilly, Pfizer and Sandoz; and consulting fees from AbbVie, Amgen, BMS, Celltrion, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis and UCB, all unrelated to this manuscript. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories among other institutions, such as Galapagos, Pfizer, Lilly, MSD, Novartis, Roche, Sanofi Aventis, BMS and Sandoz; she also reports safety board participation, not paid personally. AS reports personal fees from lectures for AbbVie, Galapagos, Lilly, Pfizer and Takeda. EFM does not report conflicts of interest. MS does not report conflicts of interest. AR does not report conflicts of interest. EH does not report conflicts of interest. JAG-P does not report conflicts of interest. MM reports having received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, all unrelated to this manuscript. PD reports speaker's fees from AbbVie, Lilly, Galapagos, Janssen and Biogen, all unrelated to this manuscript. LT does not report conflicts of interest. TG does not report conflicts of interest. MC does not report conflicts of interest. ES reports receiving grants from AbbVie; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, AbbVie, Pfizer, Eli Lilly, UCB, Sobi, Roche, Sanofi, Boehringer-Ingelheim, Viatris, Sandoz, Mylan, MSD, Amgen and Janssen-Johnson & Johnson; support for attending meetings and/or travel from AbbVie and Janssen-Johnson & Johnson; participation in a data safety monitoring board or advisory board from AbbVie, Eli Lilly, UCB, Sobi, Boehringer-Ingelheim and Janssen-Johnson & Johnson; and is a committee member of Slovak Society of Rheumatology, all unrelated to this manuscript. IB reports receiving speaker's fees from AbbVie, Pfizer, Boehringer Ingelheim and Janssen; and has received support for attending meetings and/or travel from AbbVie, all unrelated to this manuscript. ES does not report conflicts of interest. JZ reports consulting fees from AbbVie, Janssen, Novartis and Boehringer-Ingelheim; speaker's fees from AbbVie, Janssen, Novartis, Boehringer Ingelheim Latvia and UAB Viasana; receiving support for attending meetings and/or travel from AbbVie, UAB Viasana and Johnson & Johnson; and is a board member of Latvian Society of Adult Rheumatology; all unrelated to this manuscript. NR has nothing to disclose. OB has nothing to disclose. EV has nothing to disclose. BR has nothing to disclose. GRB has nothing to disclose. XM reports personal consultant fees from BMS, Galapagos, GSK, Novartis and Pfizer; and having received support for attending meetings and/or travel from Novartis, all unrelated to this manuscript. PMM has received consulting/speaker’s fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ on behalf of EULAR.)

Rational: Studies are needed to determine if multimorbidity screening and management reduce the rate of multimorbidity accumulation in patients with chronic inflammatory rheumatic diseases (IRD)., Objectives: This study evaluates the impact of systematic screening programme on patient care and hospitalisation rates., Methods: Patients with IRD who participated in the screening programme (exposed patients) were identified within the French national health database and matched with controls. Two sets of analysis were performed: one with multivariate analysis and a second using a propensity score matching to ensure comparability between exposed patients and controls. The primary endpoint (PE) was a composite score assessing the dispensation of multimorbidity-preventing drugs, including vaccines, lipid-lowering agents, antiosteoporotic medications and antiplatelet drugs, during the year following the index date., Results: The first analysis included 286 exposed patients and 858 controls, demonstrating a higher rate of meeting the PE in exposed patients (adjusted OR=1.6 (1.2-2.2), p<0.01). Propensity score matching resulted in 281 exposed patients and 281 controls. Exposed patients exhibited a significantly higher rate of meeting the PE compared with controls (54.8% vs 44.5%; OR=1.5; p=0.015), with increased utilisation of vaccines, cholesterol-lowering drugs and antiosteoporotic medications. Furthermore, emergency admission and hospitalisations for fracture, cardiovascular events or infection were significantly less frequent in the exposed group (7.1% vs 15.3%; OR=0.42, p<0.01), with a reduction in severe infections (0.7% vs 3.9%; p=0.03)., Conclusion: Systematic multimorbidity screening in patients with IRD boosted preventive medication use and reduced hospital admissions, justifying time and resource allocation for screening., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: This systematic review aimed to determine the effect of therapeutic drug monitoring (TDM) for tumor necrosis factor-α inhibitors (TNF-αI) in immune-mediated inflammatory diseases (IMIDs) based on real-world evidence, as results from published meta-analyses based on randomized controlled trials (RCTs) may not fully capture the nuances of clinical practice due to strict criteria., Methods: We searched PubMed, Embase, and the Cochrane Library up to 1 August 2023. Cohort studies comparing TDM (proactive and reactive) with empirical management were included. Primary outcome was effectiveness [for IBDs: clinical remission; for rheumatic diseases: clinical remission or low disease activity], with certainty of evidence appraised using the GRADE approach. Secondary outcomes included treatment failure, serious adverse events (SAEs), IMIDs-related surgeries or hospitalizations, and anti-drug antibodies (ADAs) development risk., Results: Twenty-four cohort studies were included and almost all were on infliximab. For IBDs, compared with empirical management, proactive TDM significantly improved clinical remission (RR = 1.15, 95% CI = 1.04-1.28), reduced IBDs-related surgeries (RR = 0.46, 95% CI = 0.26-0.81), hospitalizations (RR = 0.60, 95% CI = 0.43-0.83), SAEs (RR = 0.23, 95% CI = 0.07-0.76), and ADAs development risk (RR = 0.34, 95% CI = 0.19-0.60). Reactive TDM significantly lowered hospitalization rates and might be cost-effective. Proactive TDM outperformed reactive TDM in secondary outcomes. For rheumatic diseases, benefits of TDM were inconclusive due to limited evidence., Conclusions: Real-world evidence supports proactive TDM of TNF-αI (particularly infliximab) in IBDs to improve effectiveness, safety, and immunogenicity. However, benefits of TDM for different TNF-αI in other IMIDs remain uncertain., Protocol Registration: www.crd.york.ac.uk/ PROSPERO identifier is CRD42022370846.

Abstract: Methotrexate is one of the most frequently used medications for the treatment of rheumatic diseases. Although initially developed for use as chemotherapy for both solid and hematologic malignancies, it was used as early as the 1960s with success for rheumatoid arthritis (RA) and psoriatic arthritis, ultimately being approved by the US Food and Drug Administration for the treatment of RA in 1988. Beyond RA and psoriatic arthritis, methotrexate is used in the treatment of systemic lupus erythematosus, idiopathic inflammatory myopathies, and other inflammatory conditions. Methotrexate is cytotoxic to the trophoblast and has been used to treat both ectopic pregnancy and gestational trophoblastic neoplasia, leading to studies in the early 1990s that showed it was effective and safe for early abortion in combination with prostaglandin E1 analog misoprostol. Methotrexate is also a teratogen, causing serious birth defects in 6%-10% of patients taking it while pregnant. Additionally, women are more likely to be affected by both RA at SLE, as compared with males, thus worsening the burden of these adverse effects. Both methotrexate's history of use as an abortifacient and its teratogenic properties make its use more complicated in the current era of abortion policy in the United States following the Dobbs v. Jackson Women's Health Organization ruling. Recently published data suggest that this ruling has affected both provider perspectives and patient experiences as it relates to methotrexate use. In the post-Dobbs era, the role of the rheumatologist as it relates to patients' sexual and reproductive health is likely to expand., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Autoimmune rheumatic diseases (ARDs) often affect women during their reproductive years, and early studies of pregnancy in these patients reported high rates of adverse outcomes. Continuation or initiation of safe and effective medications in the preconception period is beneficial for maintaining or achieving disease quiescence throughout pregnancy thereby improving both maternal and pregnancy outcomes. The European Alliance of Associations for Rheumatology, the American College of Rheumatology, and the British Society for Rheumatology have published recommendations and guidelines regarding management of ARDs during pregnancy. The American College of Obstetricians and Gynecologists and the American Gastroenterological Association have also provided guidance statements with relevant recommendations. This review provides an overview of available recommendations for medication use in ARD pregnancy, with discussion of safety considerations for maternal and fetal well-being. Medications considered compatible with pregnancy include hydroxychloroquine, sulfasalazine, azathioprine, cyclosporine, tacrolimus, and TNF inhibitors. Methotrexate, mycophenolate, leflunomide, and cyclophosphamide should be avoided before and during pregnancy. Other medications, most of them newer, are largely discouraged for use in pregnancy due to inadequate data or concerns for neonatal immunosuppression, including non-TNF biologics and small molecule therapies. Further investigation is needed regarding effects of non-TNF biologics, biosimilars, and small molecules in pregnancy. Important efforts for the future will include improved methodologies to gather critical safety data, with consideration of inclusion of pregnant women in clinical trials, a complex and controversial issue. Long-term information on outcomes in offspring of treated women is lacking for many of these medications., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Contraception can help individuals with rheumatic and musculoskeletal diseases (RMDs) to avoid undesired pregnancies and improve reproductive outcomes. Despite the importance of contraception in the care of females with RMDs, evidence suggests that many of these individuals do not receive consistent or disease-specific counseling regarding contraceptive options. This includes female patients receiving teratogenic prescriptions as part of the management of their RMDs, or who have severe disease activity that might culminate in adverse pregnancy and perinatal outcomes. Contraceptive counseling can help females with RMDs who wish to prevent pregnancy to select a contraceptive method that is best for them.We conducted a narrative review of the primary literature addressing reversible, prescription-based contraception for females with RMDs, framed by published guidelines on contraceptive safety. Many safe and effective contraceptive options are available for females with RMDs. Special considerations must be given to individuals with systemic lupus erythematosus, whose disease activity may be exacerbated by exogenous estrogen. Females with positive antiphospholipid antibodies should avoid estrogen-containing contraception due to an unacceptable risk of thrombosis and should conditionally avoid depot medroxyprogesterone acetate, which appears to have a prothrombotic signature. Limited contraceptive options are available to male patients. Contraceptive care for adolescents with RMDs can be extrapolated from guidelines written for adult patients, with the additional consideration of barrier protection for individuals at risk for sexually transmitted infections. Future research is needed to assess the effects of contraception use on rheumatic disease activity and side effects., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Biologic therapies approved for treating chronic rhinosinusitis with nasal polyps (CRSwNP) have well-established safety profiles but reports of rheumatic adverse events (AEs) are increasing and not well defined. This review aims to assess the risk and incidence of rheumatic AEs associated with biologic therapy in CRSwNP and summarize current reported management strategies., Methods: A protocol was registered in PROSPERO [CRD42024525663]. A search was conducted in four electronic databases: Medline (Ovid), Embase, Scopus, and Cochrane CENTRAL from inception until January 4, 2024. Two reviewers independently screened citations and extracted data. Methodological quality was assessed using the Joanna Briggs Institute's critical appraisal tool. Data were pooled using a random effects model to calculate overall incidence and relative risk., Results: Twenty-one studies met the final inclusion criteria, totaling 3434 patients of which 2763 (80%) received either dupilumab (n = 2257; 82%), mepolizumab (n = 372; 13%), or omalizumab (n = 134; 5%) for treatment of CRSwNP. The overall incidence rate for any on-treatment rheumatic AE was 0.05 per person-year (95% CI, 0.03-0.09, I 2  = 75%). Biologic therapy increased the risk of developing a rheumatic AE (RR = 2.53; 95% CI, 1.29-4.94) compared with placebo. The most frequently reported rheumatic AE was arthralgia or joint pain (n = 94; 95%), followed by lupus-like syndrome or lupus erythematosus-like reaction (n = 2; 2.5%). Discontinuation of treatment was the most common intervention (n = 21, 39%)., Conclusion: Biologic therapy increases the risk of rheumatic AEs in CRSwNP patients by over twofold. Healthcare providers should remain vigilant in monitoring rheumatic AEs and apply appropriate management strategies on a case-by-case basis., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background: This study evaluated physicians' and patients' beliefs about biosimilars in Hong Kong, India, Pakistan, Singapore, Taiwan, and Thailand., Research Design and Methods: An online survey administered to physicians (dermatologists, n  = 119; gastroenterologists, n  = 148; rheumatologists, n  = 161) between 22 October 2021 and 7 January 2022, and patients ( n  = 90) with rheumatic or inflammatory bowel disease between 25 October 2021 and 12 April 2022., Results: Most (68%) physicians reported having a strong knowledge about biosimilars, yet 49% indicated that biosimilars are readily available to them. Physicians cited potential cost savings (81%) as the main benefit of biosimilars, and cost/coverage support (36%), patient support (25%), and increasing biosimilar awareness/education (24%) as main strategies for improving usage. Few (21%) patients reported having a strong knowledge about biosimilars. Patients cited offering alternatives in case of drug shortages (77%) as the main benefit of biosimilars, and cost/coverage support (53%), increasing awareness of product profile (22%), and providing biosimilars with a good efficacy profile/effective product (19%) as main strategies for improving usage., Conclusion: Programs focused on cost/coverage support, patient support, and biosimilar awareness could improve acceptance of biosimilars for chronic immune-mediated inflammatory diseases in Asian countries, thereby increasing patient access to essential biologic therapies.

Objective: To determine the occurrence of breakthrough COVID-19 infections (BIs) in patients with systemic lupus erythematosus (SLE) compared with patients with other rheumatic autoimmune diseases (rAIDs), patients with non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs)., Methods: The study was based on data from 7035 fully vaccinated respondents to the online COVAD questionnaire with SLE (N = 852), rAIDs (N = 3098), or nrAIDs (N = 414), and HCs (N = 2671). BI was defined as COVID-19 infection occurring in individuals vaccinated with ≥ 2 doses (or 1 dose of J&J) ≥ 14 days after vaccination and not after 6 months since the last vaccine dose. Data were analysed using linear and logistic regression models., Results: A total of 91/852 (10.7%) SLE patients reported at least one BI. The frequency of BIs in SLE patients was comparable to that among HCs (277/2671; p = 0.847) and patients with nrAID (39/414; p = 0.552) but higher than that among patients with other rAIDs (235/3098; p = 0.005). No demographic factors or treatments were associated with BIs in SLE patients (p ≥ 0.05 for all). Joint pain was more frequent in SLE patients than in HCs (odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.89-6.04; p < 0.001) or nrAID patients (OR: 2.44; 95% CI: 1.04-5.75; p = 0.041). Patient with SLE did not report a higher frequency of hospitalisation or need for advanced treatment for COVID-19 infection compared with disease controls and HCs, respectively., Conclusion: COVID-19 vaccination conferred similar protection against COVID-19 infection in terms of frequency and severity in patients with SLE to that reported by healthy individuals., (© 2024. The Author(s).)

Background and Aim: Patients with autoimmune inflammatory rheumatic disease (AIIRD) are at higher risk of severe infections because of their underlying diseases and immunosuppression. Our objective was to elucidate the epidemiological and clinical characteristics of patients with AIIRD presenting with COVID-19 and their relation to disease severity. We explored whether variables, including underlying diagnosis, disease-modifying antirheumatic drugs (DMARDs) and COVID-19 vaccine status, were associated with more severe forms of COVID-19 infection., Methods: Between 1 January 2020 and 30 June 2022, 151 patients with AIIRD and COVID-19 infection were analysed using a binary regression model and a multinomial regression model., Results: The average age was 61.5 years, and average Charlson Comorbidity Index (CCI) was 2.1; 106 (70.2%) patients were diagnosed with rheumatoid arthritis (RA), and 70 (46.4%) patients were receiving prednisolone. In the multivariable logistic regression model, ages between 50 and 69 years (odds ratio (OR) = 5.85; 95% confidence interval (CI) = 1.35-25.25) and older than 70 years (OR = 5.29; 95% CI = 1.21-23.14), prior prednisolone treatment (OR = 7.09; 95% CI = 2.63-19.11) and vaccination status including one and two doses (OR = 0.19; 95% CI = 0.05-0.69) and three and four doses (OR = 0.09; 95% CI = 0.02-0.35) were all statistically significant factors related to changes in the severity level of COVID-19., Conclusion: Severity of COVID-19 infection in patients with AIIRD is affected by age, background steroid use and vaccination status. Factors including sex, comorbidity, diagnosis of AIIRDs and use of DMARDs, including conventional synthetic, biologics and targeted DMARDs, were not significantly associated with COVID-19 severity., (© 2024 Royal Australasian College of Physicians.)

Objective: We investigated the baseline DMARD use and post-acute sequelae of COVID-19 (PASC) risk among patients with systemic autoimmune rheumatic diseases (SARDs)., Methods: Patients with SARDs and confirmed COVID-19 infection at Mass General Brigham completed a survey ≥28 days after a positive PCR/antigen test to prospectively investigate their COVID-19 courses. We investigated DMARD use at COVID-19 onset and PASC risk. PASC was defined as any COVID-19 symptom that persisted for ≥28 days. We used logistic regression to estimate the odds ratios (OR) for PASC by DMARD class. We also used restricted mean survival time to determine the difference in symptom-free days by DMARD class in the 28-day period after infection., Results: We analysed 510 patients with SARDs and COVID-19 from 11 March 2021 to 17 June 2023; 202 (40%) developed PASC. CD20 inhibitor (CD20i) users had significantly higher odds of developing PASC vs conventional synthetic DMARD (csDMARD) users [adjusted OR (aOR) 2.69 (95% CI 1.23, 5.88)]. IL-12/23, IL-17A or IL-23 inhibitor (IL-12/23i, IL-17Ai, IL-23i) users also had significantly higher odds of PASC [aOR 3.03 (95% CI 1.08, 8.49)]. CD20i users had significantly fewer symptom-free days vs csDMARD users [aOR -4.12 (95% CI -7.29, -0.94)]., Conclusion: CD20i users had significantly higher odds of PASC and fewer symptom-free days over the 28 days following COVID-19 diagnosis compared with csDMARD users. Further research is needed to investigate whether PASC risk in CD20i users may be due to prolonged infection or other immune mechanisms. The association of IL-12/23i, IL-17Ai and IL-23i with PASC calls for additional study., (© 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.)

Objectives: This study compared opioid prescribing among ambulatory visits with systemic autoimmune/inflammatory rheumatic diseases (SARDs) or without and assessed factors associated with opioid prescribing in SARDs., Methods: This cross-sectional study used the National Ambulatory Medical Care Survey between 2006 and 2019. Adult (≥18 years) visits with a primary diagnosis of SARDs, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or systemic lupus erythematosus were included in the study. Opioid prescribing was compared between those with vs without SARDs using multivariable logistic regression accounting for the complex survey design and adjusting for predisposing, enabling, and need factors within Andersen's Behavioral Model of Health Services Use. Another multivariable logistic regression examined the predictors associated with opioid prescribing in SARDs., Results: Annually, an average of 5.20 million (95% confidence interval [CI] 3.58-6.82) visits were made for SARDs, whereas 780.14 million (95% CI 747.56-812.72) visits were made for non-SARDs. The SARDs group was more likely to be prescribed opioids (22.53%) than the non-SARDs group (9.83%) (adjusted odds ratio [aOR] 2.65; 95% CI 1.68-4.18). Among the SARDs visits, patient age from 50 to 64 (aOR 1.95; 95% CI 1.05-3.65 relative to ages 18-49) and prescribing of glucocorticoids (aOR 1.75; 95% CI 1.20-2.54) were associated with an increased odd of opioid prescribing, whereas private insurance relative to Medicare (aOR 0.50; 95% CI 0.31-0.82) was associated with a decreased odds of opioid prescribing., Conclusion: Opioid prescribing in SARDs was higher compared to non-SARDs. Concerted efforts are needed to determine the appropriateness of opioid prescribing in SARDs., (© 2024 American College of Rheumatology.)

Due to optimised treatment strategies and the availability of new therapies during the last decades, formerly devastating chronic inflammatory diseases such as rheumatoid arthritis or systemic sclerosis (SSc) have become less menacing. However, in many patients, even state-of-the-art treatment cannot induce remission. Moreover, the risk for flares strongly increases once anti-inflammatory therapy is tapered or withdrawn, suggesting that underlying pathological processes remain active even in the absence of overt inflammation. It has become evident that tissues have the ability to remember past encounters with pathogens, wounds and other irritants, and to react more strongly and/or persistently to the next occurrence. This priming of the tissue bears a paramount role in defence from microbes, but on the other hand drives inflammatory pathologies (the Dr Jekyll and Mr Hyde aspect of tissue adaptation). Emerging evidence suggests that long-lived tissue-resident cells, such as fibroblasts, macrophages, long-lived plasma cells and tissue-resident memory T cells, determine inflammatory tissue priming in an interplay with infiltrating immune cells of lymphoid and myeloid origin, and with systemically acting factors such as cytokines, extracellular vesicles and antibodies. Here, we review the current state of science on inflammatory tissue priming, focusing on tissue-resident and tissue-occupying cells in arthritis and SSc, and reflect on the most promising treatment options targeting the maladapted tissue response during these diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Although the terms "rare diseases" (RD) and "orphan diseases" (OD) are often used interchangeably, specific nuances in definitions should be noted to avoid misconception. RD are characterized by a low prevalence within the population, whereas OD are those inadequately recognized or even neglected by the medical community and drug companies. Despite their rarity, as our ability on discovering novel clinical phenotypes and improving diagnostic tools expand, RD will continue posing a real challenge for rheumatologists. Over the last decade, there has been a growing interest on elucidating mechanisms of rare autoimmune and autoinflammatory rheumatic diseases, allowing a better understanding of the role played by immune dysregulation on granulomatous, histiocytic, and hypereosinophilic disorders, just to name a few. This initiative enabled the rise of innovative targeted therapies for rheumatic RD. In this review, we explore the state-of-the art of rare RD and the critical role played by rheumatologists in healthcare. We also describe the challenges rheumatologists may face in the coming decades., (© 2024. The Author(s).)

Objectives: To analyse clinical outcomes of a non-medical switch from originator adalimumab (ADA) to its ABP501 biosimilar (ABP) over 6 months in patients with inflammatory rheumatic musculoskeletal diseases (RMD) in relation to comorbidity as a risk factor for therapy discontinuation., Methods: RMD patients switching from originator ADA to ABP were identified from a large routine database from October 2018 onwards. Documented clinical data at the time of non-medical switching (baseline), and at 3 and 6 months were collected. Comorbidities were represented by the Charlson Comorbidity Index (CCI) at baseline and patients were categorized based on CCI > 0. Differences in the ABP retention rate over 6 months between patients with CCI = 0 and patients with CCI > 0 were analysed using Bayesian exponential regression., Results: A total of 111 patients with axial spondyloarthritis (n = 68), rheumatoid arthritis (n = 23) and psoriatic arthritis (n = 15), were identified, 74.8% of whom had continued treatment with ABP after 6 months, while a smaller proportion had either switched to another ADA biosimilar (10.8%), switched back to originator ADA (7.2%), switched to a different biologic (3.6%), or dropped out (3.6%). At baseline, a CCI > 0 was found in 38% of patients. Cardiovascular comorbidities (40%) were most prevalent followed by diseases of the skin (33%), the gastrointestinal tract (20%) and the eye (20%). ABP treatment was continued after 6 months in 74% of patients with CCI = 0 and in 76% with CCI > 0. Bayesian analysis showed only a small difference (months) in the APB continuation rate between groups (estimate 0.0012, 95% credible interval (CrI) -0.0337 to 0.0361). Adjusting for age, sex, and disease subtype revealed somewhat shorter retention rates for patients with CCI > 0, but the distribution of the difference included 0 (estimate -0.0689, 95% CrI -0.2246 to 0.0234)., Conclusion: In a non-medical switch scenario of RMD patients, there was no evidence for a considerable difference in ABP retention rates over 6 months between comorbidity groups., (© 2024. The Author(s).)

Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) target a specific pathway of the immune system, and are usually prescribed after failure of conventional synthetic disease-modifying antirheumatic drug therapy. The choice of b/tsDMARD depends on the disease profile and comorbidities, patient preference, registered indications of the drugs, and risks associated with therapy. It is recommended that b/tsDMARDs for immune-mediated inflammatory rheumatic diseases are prescribed by a rheumatologist, and all patients must be included in the South African Rheumatism and Arthritis Association biologic registry. Knowledge of and vigilance for adverse events, particularly infections, associated with b/ts DMARD therapies are of paramount importance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to play a major role as a severe and potentially fatal airway infection, especially in vulnerable patient groups. In view of the thin data situation on the influence of treatment and response to vaccination, at the beginning of the corona pandemic it was a major challenge to predict the tolerability and effectiveness in patients with inflammatory rheumatic diseases under immunomodulation or immunosuppression. In the meantime, numerous studies have addressed the questions of response and tolerability, at least for the COVID-19 vaccination. Even in the first months of the vaccination campaign, a small study on a single center cohort could show that apart from patients with B‑cell depletion, all included patients showed a seroconversion after the first two vaccinations. This resulted in neither an increased occurrence of exacerbations of the underlying disease nor new autoimmune phenomena. Various studies have since then confirmed these data., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Pain in the musculoskeletal system and therefore joint pain is one of the most common reasons for consulting a general practitioner (GP). Inflammatory rheumatic diseases are among the important differential diagnoses. However, the prevalence of rheumatological diseases is significantly lower than that of degenerative causes of pain. Incorrect referrals can be avoided if the causes of pain are better differentiated in GP practices. This article presents the first differential diagnostic steps that make it easier for the GP to make further treatment decisions. Physical examination, laboratory diagnostics and imaging are discussed, and the concept of "clinically suspect arthralgia" as well as the possible effects of treatment trials with glucocorticoids are presented., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Nicht‐Sponsor der Veranstaltung): nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Sponsor der Veranstaltung): nein Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objective: To identify the prevalence and clinical features of leflunomide-associated peripheral neuropathy in patients with rheumatic disease over a 42-month observational period between January 1, 2016 and June 30, 2019., Methods: A retrospective observational study was conducted using regional prescription data identifying all patients treated with leflunomide for rheumatic diseases in the Southern District Health Board of New Zealand. Medical records were used to identify patients who developed peripheral neuropathy while receiving treatment with leflunomide. Demographic characteristics, co-therapies, and additional risk factors for peripheral neuropathy were also recorded., Results: A total of 482 patients were identified as receiving leflunomide for the treatment of rheumatic during the study period. In total, 23 patients developed leflunomide-induced peripheral neuropathy within the cohort giving a prevalence of 4.7%. Nerve conduction studies (NCS) performed in 18 (78.2%) of these patients confirmed a distal axonal, sensory, or sensorimotor peripheral neuropathy. The majority of patients (n = 22; 95.6%) either improved, stabilized, or resolved on cessation of the drug, with or without medication washout. Adverse symptoms were reported in association with peripheral neuropathy in 15 of the 23 patients (65.2%): these included pain, poor sleep, compromised skin integrity, poor balance, and a Charcot-like arthropathy. Additional treatment was required to manage symptoms of peripheral neuropathy including nine patients (39%) who received pain relief., Conclusions: This study supports the previously reported association between leflunomide treatment and the development of a peripheral neuropathy. However, our findings suggest that this is more common than the previous estimates. In patients with psoriatic arthritis and previous tarsitis, there appeared to be an association with a Charcot's-like arthropathy, a complication not previously noted in the literature., (© 2024 The Author(s). International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation., Methods: Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation., Results: A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators., Conclusion: No significant differences were found between treatments in long-term survival due to inefficacy or AEs., (Copyright © 2024 by the Journal of Rheumatology.)

Background: Immune-mediated inflammatory diseases (IMIDs) typically affect women of childbearing age. One of the challenges in treating these women during pregnancy is to manage the disease while minimizing or avoiding the use of disease-modifying antirheumatic drugs (DMARDs) that may increase the risk to the mother or fetus. Biologic therapy has transformed the management of these patients. This study aimed to evaluate the maternal-fetal safety and perinatal outcomes in pregnant women with IMID exposed to biologic DMARDs either preconceptionally or during pregnancy and compare them with women using conventional DMARDs and a group of healthy pregnant women., Methods: We conducted a retrospective study with prospective follow-up of pregnant women with IMID at a single center. We analyzed baseline maternal demographic characteristics, diseases, DMARDs, and maternal-fetal outcomes., Results: A cohort of 244 pregnancies was studied. One hundred twenty-eight patients met classificatory criteria for rheumatic and musculoskeletal diseases (RMD) or inflammatory bowel disease (IBD), and 116 pregnancies of healthy women were evaluated from the same study period. One hundred and one pregnancies in IMID patients (89.84 %) occurred under immunosuppressive treatment, 78.91 % of IMID pregnancies were under cDMARD (33.59 % exclusive cDMARD), 56.25 % under bDMARD, and 27.34 % under oral glucocorticoids. Anti-TNF was the most frequent (88.88 %) bDMARD and was used in 50.78 % of the IMIDs. There was at least one flare in 37.10 % of the IMID pregnancies, and 9.38 % experienced more than one. Among flares, 43.48 % happened in the first trimester, 34.78 % in the second trimester, and 19.57 % in the third. Flares were more frequent in the RMD patients compared with IBD (p = 0.041; OR 2.15, 95%CI: 1.03-4.52). Flare was associated with discontinuation of bDMARD before the eighth week of gestation (p = 0.016), but especially in the second (p = 0.042) and third trimester (p = 0.012). Maternal infections were an infrequent complication overall (7.66 %), although more frequent in patients with IMIDs (p = 0.004) but were not associated with cDMARD or bDMARD. IMID patients needed assisted reproductive techniques (ART) more often (p = 0.001, OR 2.83, 95%CI: 1.02-7.90). More cesarean sections were performed in gestations under treatment with bDMARD (p = 0.020) and especially in those under treatment with anti-TNF. Aneuploidies calculation risk and fetal malformations were not correlated with DMARDs (cDMARDs, bDMARDs, or its combination) nor with any of the DMARDs individually preconcepcionally or during gestation. Small for gestational age (SGA) newborns were higher in patients with IMIDs however, it was not associated with DMARD use., Discussion: In general, patients with IMIDs who require treatment with bDMARDs have a more severe or refractory disease prior to gestation. In our cohort, we found a higher risk of flare among patients with bDMARDs, especially when those were suspended early. Among maternal outcomes, we found that IMID patients needed ART more often. This is probably, first of all, because of maternal age. Among fetal outcomes, there are no differences in congenital malformations in the IMIDs and healthy patients and were not correlated with DMARDs., Conclusion: The use of bDMARDs was effective in disease control and safe from a maternal-fetal point of view, with no increase in prematurity, SGA, malformations, or infections., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest concerning the research, authorship, or publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Seven of the 11 newer medications recently or soon to be approved to treat rheumatologic diseases discussed in this article are biologic agents and reflect the current ability of science to target specific components of the immune system. The other agents are molecules that are directed against specific immune pathway targets as well. All have shown superiority to placebo and in some cases have been compared to currently accepted therapies. Safety issues are generally centered around infections due to the immune-interrupting nature of these therapies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

At the beginning of the coronavirus disease 2019 (COVID-19) pandemic in December 2019 there was no available evidence regarding the management of immunosuppressive or immunomodulatory treatment and the potential outcomes of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections in inflammatory rheumatic diseases (IRD). As a result, the Justus Liebig University of Giessen, Germany, in collaboration with the German Society for Rheumatology, established the German COVID-19 register ( www.covid19-rheuma.de ). The COVID-19 register enabled for the first time a systematic documentation and evaluation of viral infections in patients with IRD. The data collection started as early as March 2020. Currently, the register is one of the largest global registers in the field of COVID-19 and IRD. As of 18 December 2023 the register has recorded more than 7100 cases. The first scientific findings on SARS-CoV‑2 infections in IRD patients were generated from the register in 2020, showing an association between disease activity of IRD, certain comorbidities, such as cardiovascular diseases and treatment with rituximab, with an unfavorable course. The contents and construction of the database of the register were designed at the conception to allow collaboration and data exchange with other national and international registers (e.g., EULAR COVID-19 register, COVID-19 global rheumatology alliance and the Lean European open survey on SARS-CoV‑2 infected patients). In addition, other registers and surveys were initiated. A vaccination register documents the tolerability and possible adverse reactions to COVID-19 vaccination in IRD patients. The data resulted in numerous publications and formed the basis for national and international recommendations for action in the care and vaccination of IRD patients during the COVID-19 pandemic. In summary, the German COVID-19 register has made a significant contribution to the understanding of the course of COVID-19 in IRD patients and has facilitated international collaboration for a better understanding of COVID-19 and IRD., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: We sought to evaluate the quality and timeliness of patient-reported outcome (PRO) measure reporting, which have not been previously studied., Methods: Clinical trials that informed new US Food and Drug Administration (FDA) approvals for the first rheumatological indication between 1995 and 2021 were identified. Data were recorded to determine whether collected PROs were published, met minimum clinically important difference (MCID) or statistical significance ( P < 0.05) thresholds, and were consistent with Consolidated Standards of Reporting Trials (CONSORT)-PRO standards. Hazard ratios and Kaplan-Meier estimate were used to assess the time from FDA approval to PRO publication., Results: Thirty-one FDA approvals corresponded with 110 pivotal trials and 262 reported PROs. Of the 90 included studies, 1 (1.1%) met all 5 recommended items, 10 (11.1%) met 4 items, 17 (18.9%) met 3 items, 21 (23.3%) met 2 items, 26 (28.9%) met 1 item, and 15 (16.7%) met none of the reporting standards. Most PROs met MCID thresholds (149/262; 56.9%) and were statistically significant (223/262; 85.1%). Of our subset analysis, one-third of PROs were not published upfront (70/212; 33%) and 1 of 9 (22/212; 10.4%) remained unpublished ≥ 4 years after initial trial reporting. Publication rates were highest for the Health Assessment Questionnaire-Disability Index (97.4%) and lowest for the 36-item Short Form Health Survey (81.8%). Less than half of these published PROs met MCID and statistical significance thresholds (94/212; 44.3%)., Conclusion: One in 9 PROs remained unpublished for ≥ 4 years after initial trial reporting, and compliance with CONSORT-PRO reporting guidelines was poor. Efforts should be made to ensure PROs are adequately reported and expeditiously published., (Copyright © 2024 by the Journal of Rheumatology.)

BLyS and APRIL have the capability to bind to B cells within the body, allowing these cells to evade elimination when they should naturally be removed. While BLyS primarily plays a role in B cell development and maturation, APRIL is linked to B cell activation and the secretion of antibodies. Thus, in theory, inhibiting BLyS or APRIL could diminish the population of aberrant B cells that contribute to SLE and reduce disease activity in patients. Telitacicept functions by binding to and neutralizing the activities of both BLyS and APRIL, thus hindering the maturation and survival of plasma cells and fully developed B cells. The design of telitacicept is distinctive; it is not a monoclonal antibody but a TACI-Fc fusion protein generated through recombinant DNA technology. This fusion involves merging gene segments of the TACI protein, which can target BLyS/APRIL simultaneously, with the Fc gene segment of the human IgG protein. The TACI-Fc fusion protein exhibits the combined characteristics of both proteins. Currently utilized for autoimmune disease treatment, telitacicept is undergoing clinical investigations globally to assess its efficacy in managing various autoimmune conditions. This review consolidates information on the mechanistic actions, dosing regimens, pharmacokinetics, efficacy, and safety profile of telitacicept-a dual-targeted biological agent. It integrates findings from prior experiments and pharmacokinetic analyses in the treatment of RA and SLE, striving to offer a comprehensive overview of telitacicept's research advancements., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Notwithstanding the wealth of literature on COVID-19, studies focusing on young adults with autoimmune diseases (AD) are lacking. To determine early (within 7 days) and late (after 7 days) anti-SARS-CoV-2 vaccine-related adverse events (AEs), post-vaccine disease flares, COVID-19 severity and breakthrough infections (B-INFs) in young people with rheumatic diseases (RMDs) and non-rheumatic autoimmune diseases (nr-ADs) compared to healthy controls (HC). Data were captured through the international COVID-19 vaccination in autoimmune diseases (COVAD) 1 and 2 questionnaires. Of 20,685 complete responses, we identified 6010 from patients aged 18-35 years (1692 RMD, 400 nrADs, 3918 HC) who received up to 4 vaccine doses. BNT162b2 was the most frequently administered vaccine and prior to vaccination, 7% of people with nrAD were taking immunosuppressants (IS) versus 80% in RMDs. Early mild AEs were more frequent in RMDs (93%) and nr-ADs (92%) compared to HC (85%). The frequency of late mild AEs was < 20% in all groups. Severe AEs were rare. SARS-CoV-2 infection rates were similar across all groups, however, RMD patients reported a single episode of infection more frequently than nrADs and HC, while nrADs reported multiple infections more frequently than RMD. Self-reported disease flares were reported by 10% or RMD and 7% of nrAD patients. Our study reinforces the safety of anti-SARS-CoV-2 vaccine also in young people with ADs, but it also highlights that among young individuals the number and clinical picture of SARS-CoV-2 infections is affected more by the type of AD rather than by coexisting IS therapy., (© 2024. The Author(s).)

Inflammatory rheumatic diseases (IRDs) refer to a range of persistent disorders that have a major influence on several physiological systems. Although there is much evidence connecting IRDs to sexual dysfunction and fertility problems, research specifically focusing on male infertility in relation to these diseases is sparse. This review addresses the complicated connection between IRDs and male infertility, emphasising the physiological, psychological, and pharmacological aspects that influence reproductive health outcomes in men with rheumatic conditions. We explore the effects of IRDs and their treatments on many facets of male reproductive well-being, encompassing sexual functionality, semen characteristics, and hormonal balance. Additionally, we present a comprehensive analysis of the present knowledge on the impact of several categories of anti-rheumatic drugs on male reproductive function. Although there is an increasing awareness of the need of addressing reproductive concerns in individuals IRDs, there is a noticeable lack of research especially dedicated to male infertility. Moving forward, more comprehensive research is needed to determine the prevalence, risk factors, and mechanisms driving reproductive difficulties in males with IRDs. We can better assist the reproductive health requirements of male IRD patients by expanding our understanding of male infertility in the setting of rheumatic disorders and implementing holistic methods to care., (© 2024. The Author(s).)

The past 25 years have seen major novel developments in the field of paediatric rheumatology. The concept of autoinflammation was introduced to this field, and medicine more broadly, with studies of familial Mediterranean fever, the most common autoinflammatory disease globally. New data on the positive evolutionary selection of familial Mediterranean fever-associated genetic variants might be pertinent to mild gain-of-function variants reported in other disease-associated genes. Genetic studies have unveiled the complexity of human heritability to inflammation and flourishing data from rare monogenic disorders have contributed to a better understanding of general disease mechanisms in paediatric rheumatic conditions. Beyond genomics, the application of other 'omics' technologies, including transcriptomics, proteomics and metabolomics, has generated an enormous dataset that can be applied to the development of new therapies and in the practice of precision medicine. Novel biomarkers for monitoring disease activity and progression have also emerged. A surge in the development of targeted biologic therapies has led to durable remission and improved prognosis for many diseases that in the past caused major complications. Last but not least, the COVID-19 pandemic has affected paediatric rheumatology practice and has sparked new investigations into the link between viral infections and unregulated inflammatory responses in children., (© 2024. Springer Nature Limited.)

Coronavirus disease 2019 (COVID-19) has influenced the world over the last 3 years. Although the risk of a severe course is low in children, it can be influenced by chronic rheumatic diseases or treatment with immunosuppressive drugs or immunomodulatory medication. The German register for biologics in pediatric rheumatology (BIKER) documented systematic data from 68 centers on the occurrence, presentation and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children with rheumatic diseases. Between March 2020 and December 2022, a total of 927 SARS-CoV‑2 infections in 884 patients could be reported and analyzed in pediatric patients with rheumatic diseases. Juvenile idiopathic arthritis (JIA) was the most frequent diagnosis (716 infections) followed by genetic autoinflammation (103 infections), systemic autoimmune diseases (78 infections), idiopathic uveitis (25 infections) and vasculitis (5 infections). Only four patients were treated as inpatients. A 3.5-year-old female patient died during the first wave from encephalopathy and respiratory failure. The patient was treated with methotrexate (MTX) and steroids for systemic JIA. Genetic tests revealed a previously unknown congenital immune defect. No other patient had to be ventilated or treated on the intensive care unit. A case of uncomplicated pediatric inflammatory multisystem syndrome (PIMS) was registered in a patient with JIA treated with MTX. At the time of the infection over 60% of the patients were treated with standard disease modifying antirheumatic drugs (DMARD) and/or biologics. Although the patients treated with MTX showed a slightly longer duration of symptoms, the antirheumatic treatment did not appear to have a negative influence on the severity or outcome of the SARS-CoV‑2 infection., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectves: Among immunosuppressants, rituximab is most strongly associated with the risk of hepatitis B virus (HBV) reactivation in chronic HBV individuals. Current guidelines recommending antiviral prophylaxis for these patients on rituximab are predominantly based on studies in oncology. However, limited data existed for the precise risk of HBV flares, effectiveness and optimal duration of antiviral prophylaxis in rituximab-treated rheumatic patients, whose immune status and treatment regimen differ significantly from those of oncology patients. Therefore, we aimed to assess the incidence and clinical outcome of HBV reactivation in HBsAg-positive patients receiving rituximab for various autoimmune diseases who discontinue the antiviral agents., Methods: A retrospective analysis was performed on 95 hepatitis B surface antigen (HBsAg)-positive patients treated with rituximab for autoimmune diseases in a single centre in Taiwan. HBV related hepatitis, defined as alanine aminotransferase (ALT) more than 3 times of baseline level and concurrent HBV reactivation, after anti-viral discontinuation, was the primary endpoint. Factors associated with HBV hepatitis flare and off-antiviral hepatitis flare were also analysed., Results: With nucleos(t)ide analogues (NA) prophylaxis, no hepatitis flares occurred. However, without prophylaxis, 59% had flare (24.5 per 100 person-years) and 8% experienced liver decompensation. Concurrent steroid use was a dose-dependent risk factor for flare. After NA discontinuation, rituximab "retreatment" led to flares in 75% of cases and liver decompensation in 63% of patients. Stopping NAs within one-year post-rituximab, even without further rituximab treatment, resulted in a 38% flare rate., Conclusions: This study offers the direct evidence for the necessity of universal antiviral prophylaxis in rheumatic patients with chronic HBV receiving rituximab. After NA discontinuation, rituximab "retreatment" led to even higher flare rate and worse outcome. Patients who completed rituximab treatment should also keep antiviral agents for at least one more year to prevent hepatitis flare.

Purpose: Rheumatologists and orthopedic surgeons frequently collaborate on difficult decisions regarding perioperative management of immunosuppression in rheumatic disease patients, balancing risk of postoperative infection with risk of disease flares. Current evidence-based guidelines pertain specifically to arthroplasty, thus we sought to understand the trends and common practices regarding peri-arthroscopic use of immunosuppression., Methods: Rheumatologists and sports medicine surgeons, from a variety of New York hospitals and serving a broad range of demographics, were surveyed on immunosuppressive medication management in rheumatic disease patients undergoing arthroscopic surgeries. Physicians' preferences were elicited regarding the use of common anti-rheumatic medications with the lower risk meniscectomies and the higher risk anterior cruciate ligament (ACL) reconstructions and allografts. Physicians were asked specifically about peri-arthroscopic use of conventional synthetic diseasemodifying antirheumatic drugs (csDMARDs), biologics, and Janus kinase (JAK) inhibitors., Results: During the survey period, 25 rheumatologists and 19 sports medicine fellowship-trained orthopedic surgeons completed the questionnaire. For lower-risk arthroscopies, rheumatologists favored continuing various csDMARDs (72% to 100%), biologics (50% to 64%) and JAK inhibitors (57%), while a majority of surgeons concurred for all three drug classes (csDMARDs 63%; biologics 53%; and JAK inhibitors 58%). For higher-risk arthroscopies, most rheumatologists preferred that patients continue csDMARDs (63% to 100%) but fewer supported the use of biologics (28% to 39%) or JAK inhibitors (22%). Surgeons were more hesitant to endorse any class of immunosuppressive antirheumatic medications (22% to 27%) around these higher risk surgeries. The rheumatologists were most concerned about surgeries taking place too soon after the last dose of rituximab, recommending these higher risk surgeries not take place for 7.7 ± 8.8 weeks following the last infusion., Conclusion: For lower-risk arthroscopies, most rheumatologists but only about half of orthopedic surgeons preferred patients continuing csDMARDs. Approximately half of both groups preferred patients hold biologics and JAK inhibitors. In more involved arthroscopies, most rheumatologists but few orthopedists supported the continued use of csDMARDs, and the consensus was to hold all other immunosuppression when possible. While the duration medications were held perioperatively were somewhat reflective of the current guidelines for arthroplasty, there is a need for evidencebased guidelines specifically regarding peri-arthroscopy immunosuppression in rheumatic disease patients.

To investigate the efficacy of the doxorubicin-etoposide-methylprednisolone, DEP) regimen as an effective treatment for adult Hemophagocytic Lymphohistiocytosis secondary to rheumatic disease and analyze prognosis in these patients. Fifty-eight adult patients diagnosed with Hemophagocytic Lymphohistiocytosis secondary to rheumatic disease admitted to Beijing Friendship Hospital from 1st Jan. 2018 to 31st Dec. 2022 were retrospectively included in this study. Patients were grouped according to previous treatment. Clinical data and laboratory characteristics of patients were retrospectively analyzed. The efficacy was evaluated every 2 weeks after initiating the first course of the DEP regimen and until the last inpatient or 31st Dec. 2023. 26 patients were included in Group A and 32 patients were included in Group B due to the previous treatment. After the first course of the DEP regimen, the overall response rate of all patients was 82.8%, with 13.8% in complete response and 69% in partial response. There was no significant statistical objective response rate between the two groups after the DEP regimen, except at 2-week. Serum ferritin, sCD25, ALT, AST, and DBIL concentrations were significantly lower at 2, 4 and 6-week than pre-treatment (P < 0.05). The overall mortality rate is 20.7% (12/58). Importantly, advanced age, initial level of HB and PLT, and central nervous system (CNS) involvement were independent poor risk factors affecting OS in bivariate analysis. The DEP regimen is effective for adult HLH secondary rheumatic disease with a high overall rate and accepted side effects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To compare the risk of gastrointestinal perforation (GIP), a rare but serious adverse event, in patients who a JAK inhibitor (JAKi; tofacitinib, baricitinib, upadacitinib, or filgotinib) versus adalimumab (tumor necrosis factor inhibitor) among a comprehensive real-world population of patients with rheumatic diseases., Methods: We conducted a nationwide population-based cohort study of the French national health data system, the exposed group that received a JAKi and the comparison group adalimumab. We included all individuals with a rheumatic disease who had their first dispensation of these treatments from July 2017 to December 2021. The primary endpoint was the occurrence of GIP (end of follow-up May 2022). Weighted hazard ratios (wHRs) were estimated with the inverse probability of treatment weighting method to account for confounding factors. Concomitant administration of systemic glucocorticoids, nonsteroidal anti-inflammatory drugs, and proton-pump inhibitors were time-varying variables., Results: The cohort included 39,758 patients: 12,335 and 27,423 in the groups that received a JAKi and adalimumab (mean age 58.2 and 47.3 years; female 76% and 58%; rheumatoid arthritis 85.3% and 27.3%, and psoriatic arthritis/axial spondyloarthritis 14.7% and 72.7%), respectively. During follow-up, 38 and 42 GIPs occurred in the groups that received a JAKi and adalimumab groups; incidence rates were 2.1 (95% confidence interval [CI] 1.5-2.8) and 1.1 (95% CI 0.8-1.5) per 1,000 person-years, respectively. Rates of GIP did not differ between the groups that received a JAKi and adalimumab: wHR 1.1 (95% CI 0.7-1.9; P = 0.65). Despite the lack of power in some subgroup analyses, results were consistent whatever the subgroup of a type of JAKi received or subgroup with a type of rheumatic disease., Conclusion: In this nationwide cohort study, the rates of GIPs did not differ between groups of patients who received JAKi and adalimumab treatment. These results need to be confirmed in other observational studies., (© 2024 American College of Rheumatology.)

Data on COVID-19 re-infections in patients with systemic rheumatic diseases (SRDs) are lacking. We aimed to describe the course and outcomes of COVID-19 re-infections in these patients versus controls. In this single-center retrospective study, we included 167 consecutive SRD patients with at least one COVID-19 re-infection (mean age 47.3 years, females 70.7%). SRD patients were compared in terms of patient-perceived COVID-19 re-infection severity and hospitalizations/deaths with 167 age/sex-matched non-SRD controls. Logistic regression analysis was performed to assess potential milder re-infection versus primary infection severity, adjusting for study group, demographics (age, sex), vaccination status, body mass index, smoking, and comorbidities. 23 and 7 out of 167 re-infected SRD patients experienced two and three re-infections, respectively, which were comparable to the re-infection rates in controls (two: 32; and three: 2) who also had comparable COVID-19 vaccination history (89% and 95% vaccinated, respectively). In the initial infection, patients with SRDs were hospitalized (7.2% versus 1.8%, p = 0.017), and had received antiviral treatment (16.1% versus 4.7%, p < 0.001) more frequently than controls. However, hospitalizations (1.8% vs 0.6%) and antiviral treatment (7.8% vs 3.5%) did not differ (p > 0.05) between patients and controls at the first re-infection, as well as during the second and third re-infection; no deaths were recorded. Perceived severity of re-infections was also comparable between patients and controls (p = 0.847) and among those on biologic DMARDs or not (p = 0.482). In multivariable analysis, neither SRDs presence nor demographics or comorbidities were associated with COVID-19 re-infection severity. COVID-19 re-infection severity (patient-perceived/hospitalizations/deaths) did not differ between SRDs and controls., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.

Background: T follicular helper (Tfh) cells are a subdivision of T helper cells involved in antigen-specific B cell immunity. Tfh cells play an essential role in the interaction of T cells/B cells in the germinal centers (GC), and dysregulation of Tfh actions can offer pathogenic autoantibody formation and lead to the development of autoimmune diseases. This study seeks to evaluate changes in Tfh frequency and its related cytokines in autoimmune disease, its association with disease phase, severity, prognosis, and the effect of immunosuppressive treatment on the Tfh population., Method: The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. Electronic databases, including PubMed, Scopus, Web of Science, and Embase, were systematically searched for potentially eligible studies up to January 1, 2024., Results: We identified 4998 articles in the initial search, from which 1686 similar titles were removed. A total of 3312 articles were initially screened, and 3051 articles were excluded by title/abstract screening. A total of 261 studies were considered for full-text assessment, and 205 articles were excluded by reason. Finally, a total of 56 studies were included in our review., Conclusion: The population of Tfh cells is generally higher in autoimmune diseases versus Health control. Moreover, the number of Tfh cells is associated with the disease severity and can be considered for determining the prognosis of studies. Also, peripheral blood circulating Tfh (cTfh) cells are an available sample that can be used as an indicator for diagnosing diseases., 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 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

This narrative review summarizes current evidence on the risk of systemic autoimmune rheumatic disease (SARD) flare following coronavirus disease 2019 vaccination. The authors detail key studies in the literature employing diverse methodologies, including cross-sectional surveys, prospective and retrospective cohorts, case-crossover designs, self-controlled case series, and systematic reviews. Data are reassuring, suggesting that vaccination is unlikely to increase the risk of flares across a range of SARD. When postvaccination flares do occur, individuals with high disease activity and frequent flares at baseline may be at higher risk. Rheumatologists may consider discussing these findings with patients during collaborative conversations about risks and benefits of vaccination., Competing Interests: Disclosure G. Braverman and M. Nong have no disclosures. M. Barbhaiya is supported by the Rheumatology Research Foundation, United States Investigator Award. L.A. Mandl receives research support from Regeneron Pharmaceuticals, United States and payments from UpToDate, unrelated to this work. L.A. Mandl works as an associate editor for Annals of Internal Medicine., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The long-term impacts of coronavirus disease 2019 (COVID-19), or post-acute sequelae of COVID-19 (PASC), are especially pertinent for individuals with systemic autoimmune rheumatic diseases, who are at higher risk of developing COVID-19 infection, complications of acute infection, and possibly PASC. Severity of acute COVID-19 infection, female sex, comorbidities, and immunosuppressive medications impact the risk of PASC in this population. The etiology of PASC remains poorly defined, and the diagnosis is clinical, with symptoms that can overlap with those of rheumatic diseases. A better understanding of the physiologic mechanisms could help to more clearly define PASC and to guide the development of targeted treatments., Competing Interests: Disclosures S. Srivatsan has no financial disclosures to report. N.J. Patel reports consulting fees from FVC Health, Alosa Health, and Arrivo Bio, and grant support from the Rheumatology Research Foundation and Amgen, all unrelated to the current work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This article provides a comprehensive review of the impact of B-cell-directed therapy on severe acute respiratory syndrome coronavirus 2 vaccine immunity, focusing on its implications in autoimmune inflammatory rheumatic diseases (AIIRD). Rituximab (RTX) is the primary B-cell-depleting drug that has been studied in AIIRD and is the focus of this review. We review the pivotal role of B cells in vaccine response and propose strategies to manage and predict vaccine responses in B-cell-depleted individuals. We highlight the need to strategize patients into distinct groups when predicting vaccine responses and developing guidelines to ensure optimal outcomes for RTX-treated patients., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)