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.

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.

Prevalence of frailty in patients with polymyalgia rheumatica and association with health-related quality of life, cognition and sarcopenia.

OBJECTIVE: To describe the prevalence of frailty in a single-centre cohort of patients with PMR and describe its association with health-related quality of life (HRQoL), cognition and sarcopenia. METHODS: This was a cross-sectional study of patients with PMR, according to 2012 EULAR/ACR Classification Criteria, presenting within 12 months of diagnosis and on treatment with glucocorticoids. Frailty was defined according to the Fried frailty criteria. HRQoL was assessed using Patient-Reported Outcomes Measurement Information System Computerized Adaptive Test (PROMIS-CAT) and cognition was assessed using the Mini-Mental State Examination. Sarcopenia was measured by DXA. RESULTS: Forty-one patients were enrolled. Prevalence of frailty and pre-frailty was 17% and 59%, respectively. Frail patients had higher inflammatory markers at diagnosis compared with pre-frail and robust patients. Of 27 patients with DXA results, 26% were sarcopenic. Frail patients had worse physical function, and more pain behaviour and interference compared with pre-frail and robust patients. In univariable analyses, frail patients were more likely to have worse physical function, and more pain behaviour and pain interference, which remained significant after adjusting for age. There were no significant associations between cognition or sarcopenia and frailty. CONCLUSIONS: In this cohort of PMR patients, there was a higher prevalence of frailty and pre-frailty compared with that reported in community-dwelling elderly. Frailty was associated with worse physical function, and increased pain behaviour and pain interference, differences that were also clinically meaningful. Larger prospective studies are needed to confirm these findings and analyse the association of frailty with other PMR disease outcomes.

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.

Clinical Features of ANCA-Associated Vasculitis in African American Patients in the United States: A Single-Center Medical Records Review Study.

BACKGROUND/PURPOSE: The aim of this study was to compare the clinical features at presentation of ANCA-associated vasculitis (AAV) between African American (AA) and White patients. METHODS: This is a chart review of cases between January 2003 and December 2018. African American patients with AAV were identified and matched in a 1:2 ratio with White comparators based on the year of diagnosis (±4 years). Data on demographics, clinical, and laboratory features and outcomes at presentation were collected. Descriptive statistics were used to compare the characteristics between groups. RESULTS: Thirty-two of 56 AA patients with AAV had complete data and were included for analysis. When compared with 64 matched White patients with AAV, AA patients were younger (47.5 vs 61.0 years, p = 0.001). Compared with White patients, AA patients with granulomatosis with polyangiitis (GPA) (35 vs 55 years, p = 0.0006) and microscopic polyangiitis (MPA) (55.5 vs 65.0 years, p = 0.05) were younger. African American patients with GPA were more frequently female (p = 0.008), whereas AA patients with MPA were more frequently male (p = 0.03). No differences in disease manifestations, disease activity, and outcomes were observed between AA and White patients with AAV. CONCLUSIONS: In this single-center study, AA patients with AAV were diagnosed at a younger age than Whites; this was found in both the GPA and MPA disease phenotypes. No other significant differences were observed. Future studies are needed to confirm our findings and better describe differences of AAV in racial/ethnic minorities.

ANCA-Associated Vasculitis in Latin America: A Systematic Literature Review: About Their Epidemiology and Their Clinical Features.

ABSTRACT: Most of the existing literature, including epidemiological studies and clinical trials, on antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) include North American (mainly United States and Canada), European, and Asian populations. Few studies have focused on multiethnic populations such as the one from Latin America. Racial and ethnic differences in the incidence of AAV could partially explain the comparatively low number of AAV studies originating in Latin America. However, given the racial/ethnic diversity as well as socioeconomic differences existing in this region, better reporting of AAV presentations and outcomes in Latin America could highlight valuable gaps on the understanding and treatment of these patients. Recently, larger case series and studies have provided better clinical information regarding AAV patients in Latin American countries; however, further information is needed to address gaps such as risk factors, genetic profiles, clinical features, and predictors of clinical outcomes. For these reasons, we have performed a systematic literature review to enhance our understanding of AAV patients in Latin America. We have included 11 articles focused on the epidemiological and clinical features of AAV in Latin America; some similarities and differences with AAV in other regions are shown in these articles. We have identified differences in their prevalence across Latin American countries, which may reflect reporting bias or true ethnic differences among the countries. Our findings should encourage further investigation into AAV in Latin America; such studies will hopefully lead to the optimal management of these patients.

The role of immunomodulatory medications in the treatment of COVID-19.

PURPOSE OF REVIEW: Given the role of inflammation in severe forms of COVID-19, glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) have been assessed as potential COVID-19 therapies. RECENT FINDINGS: Randomized controlled trials (RCTs) have shown that glucocorticoids reduce mortality in severe COVID-19. RCTs of DMARDs have shown mixed results varying on intervention and inclusion criteria. DMARDs, including colchicine or biologic agents, may improve COVID-19 outcomes in specific patient populations. SUMMARY: Glucocorticoids are an effective treatment for the management of severe COVID-19. Further studies are needed to better define the patient populations who could benefit from DMARD use, as well as provide guidance regarding the timing of these interventions.

Localized Granulomatous with Polyangiitis (GPA): Varied Clinical Presentations and Update on Treatment.

PURPOSE OF REVIEW: Granulomatosis with polyangiitis is a primary systemic vasculitis commonly described with the typical triad of upper airway, lung, and kidney involvement. Upper and lower airway involvement is characteristic in patients with granulomatosis with polyangiitis and can sometimes represent the initial or in some instances the sole manifestation. The objective of this review is to summarize the various clinical manifestations of localized disease in GPA and their treatment. RECENT FINDINGS: Sinonasal disease is seen in up to 90% of patients. Otologic and ocular involvement is also commonly seen. Laryngeal and tracheal disease although less common is associated with significant morbidity and can be therapeutically challenging. Clinicians need to be aware of these localized GPA manifestations as they may be presenting disease features in the absence of other systemic findings. Treatment of localized GPA involves both immunosuppressive and surgical interventions for specific manifestations. Collaboration between specialists including rheumatologists, otolaryngologists, and ophthalmologists is often crucial to ensure optimal outcomes for patients. This is a narrative review that provides a comprehensive overview of localized granulomatosis with polyangiitis and current treatment options.

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.

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.

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.

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.

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.

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.