Real-World Experience With Avacopan in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Introduction: Postmarketing data on outcomes of avacopan use in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are lacking. Methods: We performed a multicenter retrospective analysis of 92 patients with newly diagnosed or relapsing AAV who received therapy with avacopan. The coprimary outcome measures were clinical remission at 26 and 52 weeks. We use descriptive statistics and univariate logistic regression to assess outcomes and predictors of remission, respectively. Results: Of the 92 patients, 23% (n = 21) had a baseline estimated glomerular filtration rate (eGFR) < 15 ml/min per 1.73 m2 and 10% on kidney replacement therapy at baseline. Among those with kidney involvement, mean (SD) enrollment eGFR was 33 (27) ml/min per 1.73 m2 with a mean (SD) change of +12 (25) and +20 (23) ml/min per 1.73 m2 at weeks 26 and 52, respectively. In addition to avacopan, 47% of patients received combination therapy of rituximab and low-dose cyclophosphamide, and 14% of patients received plasma exchange (PLEX). After induction, the median (interquartile range [IQR]) time to start avacopan was 3.6 (2.1-7.7) weeks, and the median time to discontinue prednisone after starting avacopan was 5.6 (3.3-9.5) weeks. Clinical remission was achieved in 90% of patients at week 26 and 84% of patients at week 52. Of the patients, 20% stopped avacopan due to adverse events, with the most common being elevated serum aminotransferases (4.3%). Conclusion: A high rate of remission and an acceptable safety profile were observed with the use of avacopan in the treatment of AAV in this postmarketing analysis, including the populations excluded from the ADVOCATE trial.

Comparison Between Early-Onset and Common Gout: A Systematic Literature Review.

INTRODUCTION: Gout is an inflammatory, metabolic disease associated with a high comorbidity burden including cardiovascular disease, hypertension, type 2 diabetes, hyperlipidemia, renal disease, and metabolic syndrome. Approximately 9.2 million Americans have gout, making prognosis and treatment outcome predictors highly important. About 600,000 Americans have early-onset gout (EOG), generally defined as first gout attack at ≤ 40 years of age. However, data on EOG clinical features, comorbidity profile, and treatment response are sparse; this systematic literature review provides insight. METHODS: PubMed and American College of Rheumatology (ACR)/European Alliance of the Associations for Rheumatology (EULAR) abstract archives were searched for early-onset gout, "early onset gout," and ("gout" AND "age of onset"). Duplicate, foreign language, single case report, older (before 2016), and irrelevant/data insufficient publications were excluded. The age of diagnosis categorized patients as having common gout (CG, generally > 40 years) or EOG (generally ≤ 40 years). Applicable publications were extensively reviewed/discussed among authors for inclusion/exclusion consensus. RESULTS: A total of 283 publications were identified, with 46 (35 articles, 10 abstracts) reviewed and 17 (12 articles, 5 abstracts) ultimately included. Eleven reported clinical characteristics, with 6 EOG-CG retrospective/cross-sectional comparisons. Gout diagnosis preceded cardiometabolic comorbidity and renal comorbidities were less prevalent in EOG than CG patients. EOG patients had more severe disease (more gout flares, polyarticular disease), higher pre-therapy serum urate (SU), and worse oral urate-lowering therapy response. Genetics-focused publications reported higher incidences of dysfunctional urate transporter mutations in EOG patients. CONCLUSIONS: This review suggests that EOG is more recalcitrant to urate-lowering therapy, is associated with urate transporter defects, and carries heavy disease burden. Therefore, early rheumatology referral and urate-lowering in a treat-to-target fashion may benefit EOG patients. Interestingly, EOG patients had fewer cardiometabolic comorbidities at diagnosis than CG patients, presenting a potential "window of opportunity" to attenuate cardiometabolic comorbidity development with SU control. Preventing gout-related suffering and health burden is particularly important in these young EOG patients who will live with gout and its sequelae for decades.

Gout, an inflammatory arthritis caused by high urate levels in the blood (SU), is associated with medical issues, including heart disease, high blood pressure, type 2 diabetes, and kidney disease. Millions of Americans have gout, with some having early-onset gout (EOG), generally the first gout attack at or before 40 years of age. Little information on EOG has been published; this literature review provides insight. More recent articles and major rheumatology meeting presentations (2016 to August 2022) on EOG were reviewed. Publications that were duplicates, not in English, on a single patient, or were not relevant/did contain enough information were excluded. The age at gout diagnosis determined if patients had common gout (CG) or EOG. Of the 283 publications identified, 17 were included in this review. Gout-associated medical issues (heart, metabolic, and kidney-related) were less common in EOG than CG patients and occurred after gout diagnosis in EOG patients. Compared to CG patients, EOG patients more often had severe gout (more gout attacks and affected joints), higher SU, and worse response to oral SU-lowering medications. Genetics-focused publications showed that mutations affecting how urate is removed from the body are more common in EOG patients. Overall, the literature suggests that EOG may be difficult to treat, has a genetic component, and has a heavy disease burden. Therefore, early rheumatology referral and gout management may benefit EOG patients due to a potential "window of opportunity" where proper SU control may prevent gout-related suffering and health burden in young EOG patients who will live with gout and its consequences for decades.

Doxycycline-Induced Antinuclear Antibody and Antineutrophil Cytoplasmic Antibody Associated Vasculitis: A Case Report and Literature Review.

Drug-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been increasingly recognized in the literature with numerous medications listed as causative agents in disease pathology. Doxycycline is a commonly prescribed medication within the United States which is a synthetic, broad-spectrum antibiotic with antimicrobial properties and at low doses exhibits anti-inflammatory effects. In this report, we describe a case of doxycycline-induced ANCA-associated vasculitis with laboratory and biopsy findings supporting the diagnosis, which to the best of our knowledge is the first described case of doxycycline-induced AAV in the literature. The patient was started on doxycycline for treatment of potential Lyme disease. She began to develop progressively worsening myasthenia, erythematous macular rash, anorexia, anemia, and fatigue for several weeks following the course of doxycycline with initial concern of a paraneoplastic process. Ultimately, the patient was discovered to be positive for antinuclear antibody (ANA), perinuclear antineutrophil cytoplasmic antibody (pANCA), and myeloperoxidase (MPO) antibody for which she was treated with a course of prednisone leading to complete remission of disease. A brief review of the pathogenesis of ANCA vasculitides will also be discussed within this article.

Pseudogout Diagnosed By Point-of-care Ultrasound.

A 71-year-old male presented to the emergency department (ED) for worsening right knee pain for the prior 3-4 weeks. Point-of-care ultrasound (POCUS) of the right knee showed a pseudo-double contour sign. Subsequent ultrasound-guided arthrocentesis of the knee joint was performed, and fluid studies showed the presence of calcium pyrophosphate crystals, which was consistent with pseudogout. Ultrasound for detection of calcium pyrophosphate crystals in pseudogout and chondrocalcinosis has sensitivity of 86.7% and specificity of 96.4% making POCUS a valuable tool for diagnosing crystalline-induced arthropathy in the ED.