Current perspective on infections and mitigation strategies in primary systemic vasculitis.

PURPOSE OF REVIEW: The purpose of this review is to summarize and evaluate most recent evidence on the epidemiology of infections and associated risk factors in patients with primary systemic vasculitides (PSV), as well as discuss mitigation strategies including the risk of antibiotic prophylaxis. RECENT FINDINGS: Infections remain one of the leading causes of mortality in patients with PSV, with rates of severe infection ranging from 16 to 40% in different cohorts. Older age, frailty, renal and pulmonary involvement, and higher burden of comorbidities have been recognized as important patient-associated risk factors. Treatments including higher cumulative doses of glucocorticoids are associated with an increased risk of infections, and recent studies show the potential benefit of interventions such as reduced-dose glucocorticoid regimens. Existing mitigation strategies include screening, vaccination, and infection prophylaxis. The latter remains particularly important for Pneumocystis jirovecii pneumonia; however, the benefit-risk ratio seems to be less clear outside of induction phase (i.e., high dose of glucocorticoids) and optimal treatment duration remains less clear. Patients with PSV are at increased risk of infections, due to disease itself, comorbidities, and treatment side effects. Awareness of the timing and types of infection, as well as mitigation strategies are imperative to ensure treatment success and survival for patients.

Immune Checkpoint Inhibitor-induced Polymyalgia Rheumatica.

Polymyalgia rheumatica (PMR) immune-related adverse events (ICI-PMRs) represent a novel, distinct entity, despite many clinical, laboratory, and imaging similarities to classical PMR. Important questions remain in differentiating ICI-PMR from classical PMR, as well as other immune-related adverse events and PMR mimics. Despite this, ICI-PMR currently takes treatment cues from classical PMR, albeit with considerations relevant to cancer immunotherapy. Comparisons between ICI-PMR and classical PMR may provide further bidirectional insights, especially given that important questions remain unanswered about both diseases. The cause of classical PMR remains poorly understood, and ICI-PMR may represent a model of induced PMR, with important therapeutic implications.

Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment. CONCLUSION: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

Incidence of Pneumocystis Jiroveci Pneumonia in Patients With ANCA-Associated Vasculitis Initiating Therapy With Rituximab or Cyclophosphamide.

OBJECTIVE: This manuscript assesses the incidence of Pneumocystis jiroveci pneumonia (PJP) among patients receiving contemporary treatment regimens for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and adverse events associated with PJP prophylaxis. METHODS: Incident users of rituximab or cyclophosphamide for AAV were identified in the TriNetX electronic health records database from 2011 to 2022. The incidence rates (IRs) of PJP in the first 6 months of induction therapy with rituximab and/or cyclophosphamide and during postinduction maintenance therapy with rituximab were calculated. Cox proportional hazard models were used to estimate hazard ratios (HRs) and confidence intervals (CIs) for the risk of adverse events commonly associated with PJP prophylaxis. RESULTS: We identified 1,461 AAV cases who received induction therapy with rituximab (69.7%), cyclophosphamide (18.9%), or both (11.4%). Prophylaxis prescribed within 30 days of induction included trimethoprim-sulfamethoxazole (30.7%), atovaquone (5.4%), dapsone (3.8%), and pentamidine (0.8%). During induction therapy, 10 cases of PJP were identified (IR 15.0 cases per 1,000 patient-years); no deaths occurred. In adjusted analyses, those who received prophylaxis had a higher risk of leukopenia (HR 3.1; 95% CI 1.1-8.6), rash (HR 1.9; 95% CI 1.0-3.6), and nephropathy (HR 2.6; 95% CI 1.3-5.1) than those who did not. During rituximab maintenance therapy (n = 709), five cases of PJP were identified (IR 2.1 cases per 1,000 person-years), one of whom died during the hospitalization associated with a PJP diagnosis. CONCLUSION: Rates of PJP in patients with AAV were lower than previously observed, and few cases occurred during rituximab maintenance therapy. PJP prophylaxis was associated with adverse events.

Treatment of Polymyalgia Rheumatica by Rheumatology Providers: Analysis from the American College of Rheumatology RISE Registry.

OBJECTIVE: This study describes the demographics, comorbidities, and treatment patterns in a national cohort of patients with polymyalgia rheumatica (PMR) who received care from rheumatology providers. METHODS: Patients with PMR were identified in the American College of Rheumatology Rheumatology Informatics System for Effectiveness registry from 2016 to 2022. Use of glucocorticoids and immunomodulatory antirheumatic medications used as steroid-sparing agents were examined overall and in a subgroup of patients new to rheumatology practices, the majority with presumed new-onset PMR. In these new patients, multivariate logistic regressions were performed to identify factors associated with persistent glucocorticoid and steroid-sparing agent use at 12 to 24 months. RESULTS: A total of 26,102 patients with PMR were identified, of which 16,703 new patients were included in the main analysis. Patients were predominantly female (55.8%) and White (46.7%), with a mean age of 72.0 years. Hypertension (81.2%), congestive heart failure (52.4%), hyperlipidemia (41.3%), and ischemic heart disease (36.0%) were the most prevalent comorbidities. At baseline, 92.3% of patients were on glucocorticoids, and only 13.1% were on a steroid-sparing agent. At 12 to 24 months, most patients remained on glucocorticoids (63.8%). Although there was an increase in use through follow-up, antirheumatic medications were prescribed only to a minority (39.0%) of patients with PMR. CONCLUSION: In this large US-based study of patients with PMR receiving rheumatology care, only a minority of patients were prescribed steroid-sparing agents during the first 24 months of follow-up; most patients remained on glucocorticoids past one year. Further identification of patients who would benefit from steroid-sparing agents and the timing of steroid-sparing agent initiation is needed.

Recommendations for early referral of individuals with suspected polymyalgia rheumatica: an initiative from the international giant cell arteritis and polymyalgia rheumatica study group.

OBJECTIVE: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR). METHODS: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated. RESULTS: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care. CONCLUSIONS: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR.

Association of patient copayment and medication adherence in systemic lupus erythematosus.

OBJECTIVE: To investigate the association of medication copayment and treatment adherence to hydroxychloroquine and immunosuppressants for SLE. METHODS: We conducted a retrospective analysis of health claims data using Optum's de-identified Clinformatics Data Mart Database. Individuals with SLE continuously enrolled for 180 days from 1 July 2010 to 31 December 2019 were included. Adherence was defined as the proportion of days covered ≥80%. Copayment for a 30-day supply of medication was dichotomised as high (≥$10) or low (<$10). We examined the association between copayment and odds of adherence in multivariable-adjusted logistic regression models, including age, sex, race or ethnicity, comorbidities, educational attainment and household income. RESULTS: We identified 12 510 individuals (age 54.2±15.5 years; 88.2% female sex), of whom 9510 (76%) were prescribed hydroxychloroquine and 1880 (15%) prescribed hydroxychloroquine and an additional immunosuppressant (azathioprine, methotrexate or mycophenolate mofetil). Median (IQR) 30-day copayments were $8 (4-10) for hydroxychloroquine, $7 (2-10) for azathioprine, $8 (3-11) for methotrexate and $10 (5-20) for mycophenolate mofetil. High copayments were associated with OR of adherence of 0.61 (95% CI 0.55 to 0.68) for hydroxychloroquine, OR 0.44 (95% CI 0.30 to 0.66) for azathioprine and OR 0.69 (95% CI 0.49 to 0.96) for mycophenolate mofetil. For methotrexate, the association was not significant. CONCLUSION: In a large, administrative health claims database, we identified that high copayments were associated with reduced adherence to commonly prescribed medications for SLE. Incorporating awareness of the burden of copayments and its consequences into healthcare is essential to promote optimal medication adherence.

Frailty and emergency department utilisation in adults with systemic lupus erythematosus ≤65 years of age: an administrative claims data analysis of Medicaid beneficiaries.

OBJECTIVE: Frailty is a risk factor for adverse health in adults with SLE, including those <65 years. Emergency department (ED) utilisation is high in adults with SLE, but to our knowledge, whether frailty is associated with ED use is unknown. In a large administrative claims dataset, we assessed risk of ED utilisation among frail adults with SLE ≤65 years of age relative to non-frail adults ≤65 years of age with SLE. METHODS: Using the MarketScan Medicaid subset from 2011 to 2015, we identified beneficiaries 18-65 years with SLE (≥3 SLE International Classification of Diseases, Ninth Revision codes ≥30 days apart). Comparators without a systemic rheumatic disease (SRD) were matched 4:1 on age and gender. Frailty status in 2011 was determined using two claims-based frailty indices (CFIs). We compared risk of recurrent ED utilisation among frail and non-frail beneficiaries with SLE using an extension of the Cox proportional hazard model for recurrent events data. RESULTS: Of 2262 beneficiaries with SLE and 9048 non-SRD comparators, 28.8% and 11.6% were frail, respectively, according to both CFIs. Compared with non-frail beneficiaries with SLE, frail beneficiaries with SLE had significantly higher hazard of recurrent ED use (HR 1.75, 95% CI 1.48 to 2.08). CONCLUSION: Frailty increased hazard of recurrent ED visits in frail adults ≤65 years of age with SLE relative to comparable non-frail adults with SLE. Frailty is a potential target for efforts to improve quality of care in SLE.

Managing Immunosuppression in Vasculitis Patients in Times of Coronavirus Disease 2019.

The coronavirus disease 2019 (COVID-19) pandemic has led to the emergence of multiple challenges in the care of patients with systemic rheumatic diseases. Patients with vasculitis represent a group of particular concern due to existing risk factors which include a higher burden of comorbidities and specific immunosuppressive therapies used for treatment. Vaccination and the use of other risk mitigation strategies are crucial for the care of these patients. This review provides an overview of existing evidence to contribute to the understanding and specific requirements of the treatment and management of patients with vasculitis during the time of COVID-19.

An international survey of current management practices for polymyalgia rheumatica by general practitioners and rheumatologists.

OBJECTIVES: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. METHODS: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. RESULTS: In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. CONCLUSION: This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.

Is there a role for Pneumocystis jiroveci pneumonia prophylaxis in giant cell arteritis or polymyalgia rheumatica?

BACKGROUND: Pneumocystis jiroveci pneumonia (PJP) is an opportunistic fungal infection that affects immunocompromised patients. The objective of this study was to describe the incidence of PJP among patients with giant cell arteritis (GCA) or polymyalgia rheumatica (PMR). METHODS: A retrospective cohort study of incident cases of GCA and PMR was conducted using claims data from the TriNetX database to describe the incidence of PJP during the first 6 months of therapy. Additionally, a systematic review was performed to identify other publications describing PJP among patients with GCA or PMR. RESULTS: During 547 patient-years of follow-up time, no cases of PJP were identified among 1,168 cases of GCA (incident rate 0 per 1,000 person-years); during 7,446 patient-years of follow up time, one case of PJP was identified out of 15,575 cases of PMR (incident rate 0.07 cases per 1,000 patient-years). This patient was alive at last follow up. Our systematic review identified 1 case-control study, 4 cohort studies, and 18 case series / case reports of PJP among patients with GCA or PMR. The incident rate of PJP was reported from one additional study for GCA and was estimated at 0.08 cases per 1,000 person years; no additional cohort studies were identified for patients with PMR. Over the entirety of the published literature, the total number of cases identified among case series and case reports was 33, from which 4 total deaths were identified. CONCLUSIONS: Patients with newly diagnosed GCA or PMR rarely develop PJP. Existing data does not support routine prescribing of PJP prophylaxis for either group of patients.

Obstetric outcomes in women with rheumatic disease and COVID-19 in the context of vaccination status.

OBJECTIVE: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy. METHODS: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi-squared or Fisher's exact test. RESULTS: There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies, 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2% (n = 2). CONCLUSIONS: In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy.