Makol, Ashima

Abstract Objective Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys. Methods The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs. Results Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a–d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P < 0.001) and autoimmune disease multimorbidity (AIDm) (P < 0.001). In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective. A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P < 0.001). Conclusion Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.

Abstract Objective COVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys. Methods The first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analysed using regression models in different groups. Results We analysed data from 18 882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) (OR: 0.26; 95% CI: 0.24, 0.30, P < 0.001). However, concerns/fear over long-term safety had increased (OR: 3.6; 95% CI: 2.9, 4.6, P < 0.01). We noted with concern greater skepticism over vaccine science among patients with IIMs than AIRDs (OR: 1.8; 95% CI: 1.08, 3.2, P = 0.023) and HCs (OR: 4; 95% CI: 1.9, 8.1, P < 0.001), as well as more long-term safety concerns/fear (IIMs vs AIRDs – OR: 1.9; 95% CI: 1.2, 2.9, P = 0.001; IIMs vs HCs – OR: 5.4 95% CI: 3, 9.6, P < 0.001). Caucasians [OR 4.2 (1.7–10.3)] were likely to be more hesitant, while those with better PROMIS physical health score were less hesitant [OR 0.9 (0.8–0.97)]. Conclusion Vaccine hesitancy has decreased from 2021 to 2022, long-term safety concerns remain among patients with IIMs, particularly in Caucasians and those with poor physical function.

Abstract Objectives The COVID-19 vaccination in autoimmune diseases (COVAD) study aimed to assess short-term COVID-19 vaccination-related adverse events (AEs) in RA patients. Methods An online self-reported questionnaire (March–December 2021) was used to capture data related to COVID-19 vaccination-related AEs in RA, other autoimmune rheumatic diseases (AIRDs) (excluding RA and inflammatory myositis), non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs). Descriptive and multivariable regression analyses were performed. Results Of the 9462 complete respondents, 14.2% (n = 1347) had been diagnosed with RA; they had a mean (s.d.) age of 50.7 (13.7) years, 74.2% were women and 49.3% were Caucasian. In total, 76.9% and 4.2% of patients with RA reported minor and major AEs, respectively. Patients with active and inactive RA had similar AE and hospitalization frequencies. Overall, AEs were reported more frequently by BNT162b2 and mRNA-1273 recipients and less frequently by BBV152 recipients compared with the rest. Major AE and hospitalization frequencies were similar across recipients of different vaccines. Patients receiving methotrexate and hydroxychloroquine reported fewer minor AEs than those patients not on them. Compared with HCs and patients with other AIRDs, patients with RA reported similar total AEs, overall minor AEs, and hospitalizations. Compared with nrAIDs, patients with RA reported lower frequencies of overall AEs, minor AEs (both odds ratio [OR] = 0.7; 95% CI: 0.5, 0.9), and injection site pain (OR = 0.6; 95% CI: 0.5, 0.8) with similar major AE and hospitalization frequencies. Conclusion Despite the differences in AE frequency across different COVID-19 vaccines, all were well tolerated in patients with RA and were comparable to HCs, providing reassurance as to the safety of COVID-19 vaccination.

AbstractObjectivesThe assessment of physical function is fundamental in the management of patients with idiopathic inflammatory myopathies (IIMs). We aimed to investigate the physical function of patients with IIMs compared with those with non-IIM autoimmune rheumatic diseases (AIRDs) utilizing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) data obtained in the COVAD study, an international self-reported e-survey assessing the safety of COVID-19 vaccines in AIRDs.MethodsDemographics, AIRD diagnosis, disease activity, and PROMIS PF short form-10a data were extracted from the COVAD database. PROMIS PF-10a scores were compared between disease categories and stratified by disease activity. Factors affecting PROMIS PF-10a scores other than disease activity were identified by multivariable regression analysis in patients with inactive disease.ResultsA total of 1057 IIM patients, 3635 non-IIM AIRD patients and 3981 healthy controls (HCs) responded to the COVAD e-survey from April to August 2021. Using a binomial regression model, the predicted mean of PROMIS PF-10a scores was significantly lower in IIM patients compared with non-IIM AIRD patients or HCs [36.3 (95% CI 35.5, 37.1) vs 41.3 (95% CI 40.2, 42.5) vs 46.2 (95% CI 45.8, 46.6), P < 0.001], irrespective of disease activity. The independent factors for lower PROMIS PF-10a scores in patients with inactive disease were older age, female, longer disease duration, and a diagnosis of inclusion body myositis or polymyositis.ConclusionPhysical function is significantly impaired in IIMs compared with non-IIM AIRDs or HCs, even in patients with inactive disease. Our study highlights a critical need for better strategies to minimize functional disability in patients with IIMs.

AbstractIntroduction/AimsIn this study we investigated COVID‐19 vaccination–related adverse events (ADEs) 7 days postvaccination in patients with idiopathic inflammatory myopathies (IIMs) and other systemic autoimmune and inflammatory disorders (SAIDs).MethodsSeven‐day vaccine ADEs were collected in an international patient self‐reported e‐survey. Descriptive statistics were obtained and multivariable regression was performed.ResultsTen thousand nine hundred respondents were analyzed (1227 IIM cases, 4640 SAID cases, and 5033 healthy controls [HCs]; median age, 42 [interquartile range, 30‐455] years; 74% female; 45% Caucasian; 69% completely vaccinated). Major ADEs were reported by 76.3% of the IIM patients and 4.6% reported major ADEs. Patients with active IIMs reported more frequent major (odds ratio [OR], 2.7; interquartile range [IQR], 1.04‐7.3) and minor (OR, 1.5; IQR, 1.1‐2.2) ADEs than patients with inactive IIMs. Rashes were more frequent in IIMs (OR, 2.3; IQR, 1.2‐4.2) than HCs. ADEs were not impacted by steroid dose, although hydroxychloroquine and intravenous/subcutaneous immunoglobulins were associated with a higher risk of minor ADEs (OR, 1.9; IQR, 1.1‐3.3; and OR, 2.2; IQR, 1.1‐4.3, respectively). Overall, ADEs were less frequent in inclusion‐body myositis (IBM) and BNT162b2 (Pfizer) vaccine recipients.DiscussionSeven‐day postvaccination ADEs were comparable in patients with IIMs, SAIDs, and HCs, except for a higher risk of rash in IIMs. Patients with dermatomyositis with active disease may be at higher risk, and IBM patients may be at lower risk of specific ADEs. Overall, the benefit of preventing severe COVID‐19 through vaccination likely outweighs the risk of vaccine‐related ADEs. Our results may inform future guidelines regarding COVID‐19 vaccination in patients with SAIDs, specifically in those with IIMs. Studies to evaluate long‐term outcomes and disease flares are needed to shed more light on developing future COVID‐19 vaccination guidelines.

Background/Purpose: To update the epidemiology of systemic sclerosis and evaluate the performance of the American College of Rheumatology/European League Against Rheumatism 2013 versus 1980 American Rheumatism Association classification criteria in a US population-based cohort. Methods: An inception cohort of patients with incident systemic sclerosis from 1 January 1980 through 31 December 2018, in Olmsted County, Minnesota, was identified based on comprehensive individual medical record review. Incidence and prevalence rates were age- and sex-adjusted to the 2010 US white population. Survival rates were compared with expected rates in the general population. Fulfillment of 1980 and 2013 classification criteria was ascertained. Results: A total of 85 incident cases of systemic sclerosis (91% female, mean age = 55.4 ± 16 years) and 49 prevalent cases on 1 January 2015 were identified. The overall age- and sex-adjusted annual incidence was 25 (95% confidence interval = 20–31) per million population, with no change in incidence over time. The age- and sex-adjusted prevalence was 436 (95% confidence interval = 313–558) per 1,000,000 population. 77 (91%) patients fulfilled the 2013 classification criteria, and 38 (45%) fulfilled the 1980 criteria. Mortality among patients with systemic sclerosis was significantly higher in comparison to the general population, with a standardized mortality ratio of 2.48 (95% confidence interval = 1.76–3.39) and no evidence of improvement over time. Conclusion: Systemic sclerosis developed in 25 persons/million/year with no change over the 39-year study period. The 2013 classification criteria perform significantly better than the 1980 criteria but failed to classify 9% of patients. Systemic sclerosis portends a 2.5-fold higher risk of mortality than the general population, with no evidence of improved survival over time.

INTRODUCTION: Intestinal pseudo-obstruction is characterized by impaired transit and luminal dilation in the absence of mechanical obstruction. Our study aims to describe the clinical, radiographic, and physiological findings in pseudo-obstruction associated with systemic sclerosis (SSc), amyloidosis, and paraneoplastic syndrome. METHODS: A retrospective cohort of patients evaluated at our institution between January 1, 2008, and August 1, 2018, was assembled. Clinical, imaging, and physiological characteristics were abstracted from electronic medical records. RESULTS: We identified 100 cases of pseudo-obstruction (55 SSc, 27 amyloidosis, and 18 paraneoplastic). Female population predominance was seen in SSc (71%) vs male population in amyloidosis (74%). Most common symptom was abdominal bloating in all 3 groups. Vomiting was more common in SSc than amyloidosis (73% vs 46%, P = 0.02). Diarrhea was more common in amyloidosis and SSc compared with paraneoplastic (81% and 67% vs 28%, P < 0.01). Weight loss (>5%) was more common in SSc compared with amyloidosis and paraneoplastic (78% vs 31% and 17%, P < 0.0001). Only small bowel dilation was seen in 79%, 40%, and 44% and only large bowel dilation in 2%, 44%, and 44% of patients in SSc, amyloidosis, and paraneoplastic, respectively. Five of 8 SSc patients had myopathic and 3 of 5 paraneoplastic had neuropathic involvement on gastroduodenal manometry. DISCUSSION: SSc-associated pseudo-obstruction demonstrates female population predominance and presents with vomiting, diarrhea, and weight loss. Amyloidosis-associated pseudo-obstruction shows male population predominance. Small bowel is more commonly involved than large bowel on both imaging and transit studies in SSc. Myopathic involvement was more common in SSc, contrary to neuropathic in paraneoplastic syndrome.

Systemic sclerosis (SSc) is characterised by non-inflammatory vasculopathy, autoimmunity and widespread fibrosis. While the presence of antineutrophil cytoplasmic antibodies (ANCAs) has been reported in SSc, their association with ANCA-associated vasculitis is exceedingly rare. Myeloperoxidase ANCA is more common than proteinase-3 ANCA, and glomerulonephritis is the most common clinical presentation of ANCA-associated vasculitis in SSc. ANCAs have been associated with the adverse disease outcomes in SSc, including higher mortality per recent reports. A 65-year-old man with diffuse cutaneous SSc for 6 years presented with new-onset peripheral neuropathy. Workup revealed a positive proteinase-3 and cytoplasmic ANCA, and histopathology confirmed an inflammatory vasculitic neuropathy. The patient was successfully treated with rituximab. Our case highlights the importance of checking ANCA in SSc at baseline, given the risk of disease-related complications, even years later. Tissue biopsy is often warranted for confirmation of vasculitis and prompt treatment can optimise long-term outcomes.