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.

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.

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.

Incidence of dementia in patients with rheumatoid arthritis and association with disease modifying anti-rheumatic drugs - Analysis of a national claims database.

OBJECTIVE: To evaluate the risk of incident dementia associated with the use of biologics or targeted synthetic DMARDs (b/tsDMARD) compared to conventional synthetic (cs) DMARDS only in patients with rheumatoid arthritis (RA). METHODS: We analyzed claims data from the Center for Medicare & Medicare Services (CMS) from 2006-2017. Patients with RA were identified as adults ≥40 years old and two RA diagnoses by a rheumatologist > 7 and < 365 days apart. Patients with a prior diagnosis of dementia were excluded. Use of cs/b/tsDMARDs was the exposure of interest. Person-time was classified as either: 1) b/tsDMARD exposed, which included tumor necrosis factor alpha inhibitors (TNFi)-bDMARDs, non-TNFi-bDMARDs or tsDMARDs with or without csDMARDs; 2) csDMARD-exposed: any csDMARD without b/tsDMARD. Patients could contribute time to different exposure groups if they changed medications. Incident dementia was defined as: 1 inpatient OR 2 outpatients ICD-9-CM or ICD-10 claims for dementia, OR prescription of a dementia-specific medication (rivastigmine, galantamine, memantine, donepezil, tacrine). Age-adjusted incident rates (IR) were calculated, and univariate and multivariate Cox proportional hazard models were used to calculate Hazard Ratios (HR) and 95% confidence intervals (CI). RESULTS: We identified 141,326 eligible RA patients; 80% female and 75.3% white, median age 67 years and mean (SD) exposure time of 1.1 (1.5) years. There were 233,271 initiations of c/b/tsDMARDS and 3,794 cases of incident dementia during follow up. The crude IR of dementia was 2.0 (95% CI 1.9-2.1) per 100 person-years for patients on csDMARDs and 1.3 (95% CI 1.2-1.4) for patients on any b/tsDMARD. Patients on b/tsDMARDs had an adjusted 19% lower risk for dementia than patients on csDMARDs [HR 0.81 (95% CI 0.76-0.87)]. Subgroup analysis found comparable risk reductions between TNFi, non-TNFi, and tsDMARDs. on the risk of dementia. CONCLUSIONS AND RELEVANCE: The incidence of dementia in patients with RA was lower in patients receiving b/tsDMARDs when compared to patients on csDMARD only. No differences were observed between different classes of b/tsDMARDs, suggesting that decreased risk is possibly explained by the overall decrease in inflammation rather than a specific mechanism of action of these drugs.

Prolonged COVID-19 symptom duration in people with systemic autoimmune rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.

OBJECTIVE: We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs). METHODS: We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021-15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression. RESULTS: We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81). CONCLUSION: Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs.

Comparing cardiovascular risk of patients with rheumatoid arthritis within the Social Security Disability Insurance with those commercially insured.

OBJECTIVE: To compare cardiovascular disease (CVD) rates in rheumatoid arthritis (RA) beneficiaries of the Social Security Disability Insurance (SSDI) with commercially insured RA patients. METHOD: We created three cohorts of RA patients aged < 65 years for SSDI and three for Marketscan using claims data from 2006 to 2016. The cohort definitions were as follows: (1) cohort 1: ≥ 2 diagnosis codes for RA occurring 7-365 days apart with ≥ 1 diagnosis code from a rheumatologist; (2) cohort 2: ≥ 1 diagnosis code for RA from a rheumatologist and a disease-modifying antirheumatic drugs (DMARDS); and (3) cohort 3: cohort 2, plus initiation of a new biologic/tofacitinib. We used Cox regression to determine the CVD risk comparing SSDI vs. Marketscan. Models were sequentially adjusted for age and sex (model 1); model 1 + diabetes, smoking, and high CVD risk (model 2); and model 2 + dual eligible (Medicare and Medicaid), subsidy, and state buy in (model 3). RESULTS: There were 380,336 RA patients, mean age 53.3 (SD 8.1) years, 21-24% male. Prevalence of comorbidities was higher in SSDI vs. Marketscan. SSDI RA patients in cohort 2 (model 3) had higher CVD risk (HR 1.23 (1.14-1.33). In cohort 3 (model 3), CVD risk was not statistically significantly different between SSDI and Marketscan (HR 0.89 (0.69-1.15). CONCLUSION: RA patient beneficiaries of the SSDI had higher risk for CVD events than those employed. The differences in CVD events between SSDI and Marketscan were partially attributable to differences in CVD risk factors.

Baseline factors associated with self-reported disease flares following COVID-19 vaccination among adults with systemic rheumatic disease: results from the COVID-19 global rheumatology alliance vaccine survey.

OBJECTIVE: To examine the frequency of, and risk factors for, disease flare following COVID-19 vaccination in patients with systemic rheumatic disease (SRD). METHODS: An international study was conducted from 2 April to 16 August 2021, using an online survey of 5619 adults with SRD for adverse events following COVID-19 vaccination, including flares of disease requiring a change in treatment. We examined risk factors identified a priori based on published associations with SRD activity and SARS-CoV-2 severity, including demographics, SRD type, comorbidities, vaccine type, cessation of immunosuppressive medications around vaccination and history of reactions to non-COVID-19 vaccines, using multivariable logistic regression. RESULTS: Flares requiring a change in treatment following COVID-19 vaccination were reported by 4.9% of patients. Compared with rheumatoid arthritis, certain SRD, including systemic lupus erythematosus (OR 1.51, 95% CI 1.03, 2.20), psoriatic arthritis (OR 1.95, 95% CI 1.20, 3.18) and polymyalgia rheumatica (OR 1.94, 95% CI 1.08, 2.48) were associated with higher odds of flare, while idiopathic inflammatory myopathies were associated with lower odds for flare (OR 0.54, 95% CI 0.31-0.96). The Oxford-AstraZeneca vaccine was associated with higher odds of flare relative to the Pfizer-BioNTech vaccine (OR 1.44, 95% CI 1.07, 1.95), as were a prior reaction to a non-COVID-19 vaccine (OR 2.50, 95% CI 1.76, 3.54) and female sex (OR 2.71, 95% CI 1.55, 4.72). CONCLUSION: SRD flares requiring changes in treatment following COVID-19 vaccination were uncommon in this large international study. Several potential risk factors, as well as differences by disease type, warrant further examination in prospective cohorts.