Value of isolated IgA anti-ß2 -glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome.

OBJECTIVE: To examine the prevalence of isolated IgA anti-ß2 -glycoprotein I (anti-ß2 GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of ß2 GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-ß2 GPI in a mouse model of thrombosis. METHODS: Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-ß2 GPI titers and binding to domain IV/V of ß2 GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-ß2 GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity. RESULTS: A total of 198 patients were found to be positive for IgA anti-ß2 GPI isotype, and 57 patients were positive exclusively for IgA anti-ß2 GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-ß2 GPI-positive serum samples reacted with domain IV/V of anti-ß2 GPI, and 77% of those had clinical features of APS. Isolated IgA anti-ß2 GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-ß2 GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-ß2 GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. CONCLUSION: Isolated IgA anti-ß2 GPI-positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-ß2 GPI antibodies directed to domain IV/V of ß2 GPI represent an important subgroup of clinically relevant antiphospholipids.

Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis.

It has been recently demonstrated that interleukin 1ß (IL-1ß) plays a central role in monosodium urate crystal-induced inflammation and that the NALP3 inflammasome plays a major role in IL-1ß production. These discoveries have offered new insights into the pathogenesis of acute gouty arthritis. In this review, we discuss the molecular mechanisms by which monosodium urate crystals induce acute inflammation and examine the mechanisms of action (MOAs) of traditional anti-inflammatory drugs (e.g., nonsteroidal anti-inflammatory drugs, colchicine, and glucocorticoids) and biologic agents (e.g., the IL-1ß antagonists anakinra, rilonacept, and canakinumab) to understand how their MOAs contribute to their safety profiles. Traditional anti-inflammatory agents may act on the IL-1ß pathway at some level; however, their MOAs are broad-ranging, unspecific, and biologically complex. This lack of specificity may explain the range of systemic adverse effects associated with them. The therapeutic margins of nonsteroidal anti-inflammatory drugs, colchicine, and glucocorticoids are particularly low in elderly patients and in patients with cardiovascular, metabolic, or renal comorbidities that are frequently associated with gouty arthritis. In contrast, the IL-1ß antagonists act on very specific targets of inflammation, which may decrease the potential for systemic adverse effects, although infrequent but serious adverse events (including infection and administration reactions) have been reported. Because these IL-1ß antagonists target an early event immediately downstream from NALP3 inflammasome activation, they may provide effective alternatives to traditional agents with minimal systemic adverse effects. Results of ongoing trials of IL-1ß antagonists will likely provide clarification of their potential role in the management of acute gouty arthritis.

Characteristics of Patients with Psoriatic Arthritis Receiving Secukinumab and Reasons for Initiation: A US Retrospective Medical Chart Review.

INTRODUCTION: Secukinumab is a fully human anti-interleukin 17A monoclonal antibody approved for the treatment of psoriatic arthritis (PsA) in the United States. Few studies have investigated prescribing patterns among rheumatologists who have initiated secukinumab for the treatment of patients with PsA in real-world settings. This US medical chart review describes clinical and treatment characteristics of patients with psoriatic arthritis (PsA) who were prescribed secukinumab and rheumatologist-reported reasons for prescribing secukinumab in clinical practice. METHODS: This US medical chart review included patients with physician-diagnosed PsA aged ≥ 18 years initiating secukinumab after January 15, 2016. Eligible rheumatologists used online forms to collect patient demographics, disease characteristics, comorbidity profiles, and treatment histories before or on the date of the first secukinumab prescription recorded in the medical chart. Information on reasons for secukinumab prescription and dosing was also collected. RESULTS: Medical charts from 153 patients with PsA who initiated secukinumab were reviewed by 46 rheumatologists between July 7, 2017, and August 11, 2017. Overall, 53.6% of patients were male, mean (standard deviation) age was 47.3 (11.5) years, and 24.8% were biologic naive. The most common reasons for secukinumab prescription among biologic-naive and biologic-experienced patients, respectively, were efficacy/effectiveness of secukinumab (84.2%) and failure of other prior biologics (80.9%). Nearly all patients (94.1%) received a loading regimen, including 150 mg every week (32.7%) and 300 mg every week (61.4%). Overall, 145 patients (94.8%) received ≥ 1 maintenance dose, of whom 49.7% received 150 mg every 4 weeks and 50.3% received 300 mg every 4 weeks. CONCLUSIONS: At the time of the chart review, most patients with PsA who initiated secukinumab were biologic experienced, although one-quarter received secukinumab as first-line biologic therapy. Efficacy/effectiveness of secukinumab and failure of other biologics were the most common reasons for initiating secukinumab. FUNDING: Novartis Pharmaceuticals Corporation, East Hanover, NJ. Plain language summary available for this article.

Characterization of Patients with Ankylosing Spondylitis Receiving Secukinumab and Reasons for Initiating Treatment: A US Physician Survey and Retrospective Medical Chart Review.

OBJECTIVES: To characterize US patients with ankylosing spondylitis (AS) who were treated with secukinumab and to assess rheumatologist-reported reasons for prescribing treatment in clinical practice. METHODS: This descriptive analysis of data from a US retrospective medical chart review included patients aged ≥ 18 years diagnosed with AS who initiated secukinumab after 15 January 2016. Eligible rheumatologists used online forms to collect patient demographics, disease characteristics, co-morbidity profile, and treatment history prior to or on the index date, defined as the date of the first secukinumab prescription recorded in the medical chart. Information on physician-level characteristics and reasons for secukinumab prescription and dosing were also collected. RESULTS: Medical charts from 78 patients with AS who initiated secukinumab were reviewed by 25 rheumatologists between 7 July 2017 and 11 August 2017. Overall, 76.9% of patients were male, mean (SD) age was 39.8 (10.8) years, and 34.6% were biologic naïve. The most common reasons for secukinumab initiation among biologic-naïve and biologic-experienced patients, respectively, were efficacy/effectiveness (77.8%) and failure of other prior biologics (84.3%). Nearly all patients (94.9%) received a loading dose, including 150 mg every week (39.7%), 300 mg every week (53.8%), and other (1.3%). Overall, 73 patients (93.6%) received ≥ 1 maintenance secukinumab dose, of whom 56.2% and 43.8% received 150 mg and 300 mg, respectively, every 4 weeks. CONCLUSIONS: In this US medical chart review of patients with AS who initiated secukinumab, approximately one-third were biologic naïve, and secukinumab efficacy/effectiveness and failure of other biologics were the most common reasons for initiating secukinumab.

Using Self-Reported Patient Experiences to Understand Patient Burden: Learnings from Digital Patient Communities in Ankylosing Spondylitis.

INTRODUCTION: Online communities contain a wealth of information containing unsolicited patient experiences that may go beyond what is captured by guided surveys or patient-reported outcome (PRO) instruments used in clinical settings. This study described patient experiences reported online to better understand the day-to-day disease burden of ankylosing spondylitis (AS). METHODS: Unguided, English-language patient narratives reported between January 2010 and May 2016 were collected from 52 online sources (e.g., general/health social networking sites, patient-physician Q&A sites, AS forums). Using natural language processing combined with manual curation, patient-reported experiences within narratives were evaluated and categorized into social, physical, emotional, cognitive, and role activity (SPEC-R) concepts to assess functional impairment. The same SPEC-R categorization was applied to 5 AS-specific PRO instruments to evaluate their coverage of concepts extracted from patient narratives. RESULTS: A total of 34,780 narratives from 3449 patients with AS were included. Physical aspects of AS (e.g., pain and mobility) were most commonly reported by patients (86.7%), followed by emotional (32.5%), cognitive (23.6%), role activity (8.7%) and social (5.1%). Some frequently discussed subconcepts were effectively captured by ≥ 2 PRO instruments, such as pain (65.3%), asthenia (19.9%), musculoskeletal impairment (19.9%), depression (9.9%), and anger/frustration (5.4%); others [e.g., anxiety (19.1%), mental impairment (3.2%), impulsivity (2.9%)] were not addressed by any of the PRO instruments. CONCLUSION: These findings highlight the importance of analyzing patient experiences beyond clinical trial settings and physician reports; continuous assessment of existing PRO instruments in collaboration with patients may increase their utility in real-world settings. FUNDING: Novartis Pharmaceuticals Corporation.

Evaluation of Self-reported Patient Experiences: Insights from Digital Patient Communities in Psoriatic Arthritis.

OBJECTIVE: To evaluate the types of experiences and treatment access challenges of patients with psoriatic arthritis (PsA) using self-reported online narratives. METHODS: English-language patient narratives reported between January 2010 and May 2016 were collected from 31 online sources (general health social networking sites, disease-focused patient forums, treatment reviews, general health forums, mainstream social media sites) for analysis of functional impairment and 40 online sources for assessment of barriers to treatment. Using natural language processing and manual curation, patient-reported experiences were categorized into 6 high-level concepts of functional impairment [social, physical, emotional, cognitive, role activity (SPEC-R), and general] and 6 categories to determine barriers to treatment access (coverage ineligibility, out-of-pocket cost, issues with assistance programs, clinical ineligibility, formulary placement/sequence, doctor guidance). The SPEC-R categorization was also applied to 3 validated PsA patient-reported outcome (PRO) instruments to evaluate their capacity to collect lower-level subconcepts extracted from patient narratives. RESULTS: Of 15,390 narratives collected from 3139 patients with PsA for exploratory analysis, physical concepts were the most common (81.5%), followed by emotional (50.7%), cognitive (20.0%), role activity (8.1%), and social (5.6%) concepts. Cognitive impairments and disease burden on family and parenting were not recorded by PsA PRO instruments. The most commonly cited barriers to treatment were coverage ineligibility (51.6%) and high out-of-pocket expenses (31.7%). CONCLUSION: Patients often discussed physical and emotional implications of PsA in online platforms; some commonly used PRO instruments in PsA may not identify cognitive issues or parenting/family burden. Nearly one-third of patients with PsA reported access barriers to treatment.

Gouty arthritis: understanding the disease state and management options in primary care.

Acute gouty arthritis is an inflammatory response triggered by the release of monosodium urate crystal deposits into the joint space. The disease is associated with debilitating clinical symptoms and functional impairments as well as adverse economic and quality-of-life burdens. Because gouty arthritis is typically diagnosed and managed in the primary care setting, clinicians require a thorough knowledge of the presenting clinical features, risk factors, differential diagnoses, and treatment options for appropriate management. Although generally effective, the use of currently available therapies to control gouty arthritis is challenging because many medications used to treat comorbidities can exacerbate gouty arthritis and because current agents are associated with a number of adverse events, contraindications, or both. Based on an understanding of the underlying inflammatory pathogenesis of gouty arthritis, several new agents are being developed that may provide improved efficacy.

Eosinophilic enteritis with systemic lupus erythematosus.

Gastrointestinal manifestations are common in systemic lupus erythematosus (SLE). Eosinophilic enteritis is a rare disorder of uncertain cause that was recently reported for the first time in association with SLE. This report presents a second case of eosinophilic enteritis in a 47-year-old female patient with SLE. The patient presented with recurrent episodes of abdominal pain, nausea, vomiting, and diarrhea. Complete blood counts on occasion showed elevated eosinophil counts. The patient underwent a comprehensive workup over several weeks, culminating in a small bowel biopsy that showed eosinophil infiltration in the muscularis propria, establishing the diagnosis. The patient was treated with a prolonged taper of prednisone with successful resolution of symptoms.