A Large Cluster of New Onset Autoimmune Myositis in the Yorkshire Region Following SARS-CoV-2 Vaccination.

BACKGROUND: The novel SARS-CoV-2 vaccines partially exploit intrinsic DNA or RNA adjuvanticity, with dysregulation in the metabolism of both these nucleic acids independently linked to triggering experimental autoimmune diseases, including lupus and myositis. METHODS: Herein, we present 15 new onset autoimmune myositis temporally associated with SARS-CoV-2 RNA or DNA-based vaccines that occurred between February 2021 and April 2022. Musculoskeletal, pulmonary, cutaneous and cardiac manifestations, laboratory and imaging data were collected. RESULTS: In total, 15 cases of new onset myositis (11 polymyositis/necrotizing/overlap myositis; 4 dermatomyositis) were identified in the Yorkshire region of approximately 5.6 million people, between February 2021 and April 2022 (10 females/5 men; mean age was 66.1 years; range 37-83). New onset disease occurred after first vaccination (5 cases), second vaccination (7 cases) or after the third dose (3 cases), which was often a different vaccine. Of the cases, 6 had systemic complications including skin (3 cases), lung (3 cases), heart (2 cases) and 10/15 had myositis associated autoantibodies. All but 1 case had good therapy responses. Adverse event following immunization (AEFI) could not be explained based on the underlying disease/co-morbidities. CONCLUSION: Compared with our usual regional Rheumatology clinical experience, a surprisingly large number of new onset myositis cases presented during the period of observation. Given that antigen release inevitably follows muscle injury and given the role of nucleic acid adjuvanticity in autoimmunity and muscle disease, further longitudinal studies are required to explore potential links between novel coronavirus vaccines and myositis in comparison with more traditional vaccine methods.

Abatacept reduces disease activity and ultrasound power Doppler in ACPA-negative undifferentiated arthritis: a proof-of-concept clinical and imaging study.

OBJECTIVES: No proven treatment exists for ACPA-negative undifferentiated arthritis (UA). The aim of this study was to evaluate whether abatacept is effective in treating poor prognosis, ACPA-negative UA, including its effect on power Doppler on US (PDUS). METHODS: A proof-of-concept, open-label, prospective study of 20 patients with DMARD-naïve, ACPA-negative UA (⩾2 joint synovitis) and PDUS ⩾ 1 with clinical and 20-joint US (grey scale/PDUS) assessments at baseline, 6, 12, 18 and 24 months. All patients received 12 months of abatacept (monotherapy for minimum first 6 months). The primary end point was a composite of the proportion of patients that at 6 months achieved DAS44 remission, a maximum of one swollen joint for at least 3 consecutive months and no radiographic progression (over 0-12 months). RESULTS: Twenty of the 23 patients screened were enrolled [14 female; mean (sd) age 53.4 (11.2) years, symptom duration 7.5 (0.9) months]. Two (10%) achieved the composite primary end point. A reduction in the mean (sd) DAS44 was observed from a baseline value of 2.66 (0.77) to 2.01 (0.81) at 6 months and to 1.78 (0.95) at 12 months. The DAS44 remission rates were 6/20 (30%; 95% CI: 15, 51%) at 6 months and 8/20 (40%; 95% CI: 22, 62%) at 12 months. A striking decrease in the median (interquartile range; IQR) total PDUS score was noted from 10 (4-23) at baseline to 3 (2-12) and 3 (0-5) at 6 and 12 months, respectively. CONCLUSION: This report is a first in potentially identifying an effective therapy, abatacept monotherapy, for poor-prognosis, ACPA-negative UA, supported by a clear reduction in PDUS. These data justify evaluation in a controlled study.

The effect of prior bisphosphonate therapy on the subsequent BMD and bone turnover response to strontium ranelate.

Strontium ranelate is an effective treatment for osteoporosis in treatment-naive women. In the United Kingdom, bisphosphonates are often used first line. Prior bisphosphonate use may blunt the bone mineral density (BMD) response to strontium ranelate by reducing strontium uptake into the bone. Sixty bisphosphonate-naive women and 60 women discontinuing bisphosphonates were recruited. All women commenced strontium ranelate and calcium/vitamin D. BMD and bone turnover markers were recorded for 12 months. After 12 months, the bisphosphonate-naive group's BMD increased by 5.6% (p < .001) at the spine, 3.4% (p < .001) at the total hip, and 4.0% (p < .001) at the heel. By comparison, the prior bisphosphonate group had a 2.1% (p = .002) increase at the spine but no change at the hip or heel. At all time points, BMD was significantly greater in the bisphosphonate-naive group. In the prior bisphosphonate group, there was no significant change in BMD during the first 6 months at the spine, but between months 6 and 12 there was a parallel gain in BMD (0.027 versus 0.020 g/cm(2), p = .40). The baseline difference in bone markers was no longer significant by 3 months for bone-specific alkaline phosphatase (BSAP) and 6 months for procollagen type 1 amino-terminal propeptide (P1NP) and carboxy-terminal cross-linking telopeptide of type I collagen (CTX). More women in the prior bisphosphonate group suffered a vertebral fracture (2 versus 8 women, p = .047). After bisphosphonates, bone turnover remains suppressed for up to 6 months, with blunting of the BMD response to strontium ranelate during this time. After 6 months, BMD increases in the spine but not at the hip or heel.

Which women should be selected for vertebral fracture assessment? Comparing different methods of targeting VFA.

Vertebral fracture assessment (VFA) is a potential screening tool for vertebral fractures, but it is uncertain how to optimize the selection of women for VFA. We investigate the use of a probability score (VFscore) to select women for VFA screening and compare this to other means of targeting VFA. We identified 1,572 treatment-naive women over age 65 who had undergone routine VFA screening. Risk factors for fracture on VFA were identified using multivariate logistic regression, and a VFscore was created. Different thresholds of VFscore were examined and compared to using BMD as a means of targeting screening. After multivariate logistic regression, the risk factors significantly associated with the presence of a fracture on VFA were age, femoral neck BMD, prior clinical fracture, and height loss/kyphosis. The VFscore derived from these factors had a 65.5% sensitivity and a 65.5% specificity for determining vertebral fracture status. For equal resource requirements, the VFscore identified more women with fracture than using BMD category to target VFA. Compared to routinely screening all women, VFscore enabled a 30% reduction in the number of women undergoing VFA while still identifying >90% of women with a vertebral fracture. Overall, a large proportion of the population is required to undergo VFA in order to ensure that the majority of women with a vertebral fracture are selected for screening. The VFscore increased the efficiency of VFA screening to a modest degree compared to screening routinely or according to BMD category.

The effect of prior bisphosphonate exposure on the treatment response to teriparatide in clinical practice.

Our objective was to determine the effect of prior bisphosphonate exposure on the treatment response to teriparatide. All patients started on teriparatide in our hospital are entered into a database. All patients who had at least 12 months' treatment were identified. Patients were divided into two groups depending on whether or not they had prior bisphosphonate exposure, and the response to teriparatide was compared using procollagen of type 1 N-terminal propeptide (P1NP) and bone mineral density (BMD). Fifty-two patients had been treated for at least 12 months, 38 with prior bisphosphonate exposure and 14 without. The mean duration of bisphosphonate treatment was 67 months, discontinued a mean of 1 month previously. P1NP increased significantly at 3 and 6 months in both groups. However, those without previous bisphosphonate treatment had a higher baseline P1NP (49 vs. 30 microg/L, P<0.01), and this remained higher at 3 months (109 vs. 71 microg/L, P=0.10) and 6 months (183 vs. 126 microg/L, P=0.06), although the difference was not significant. In the prior bisphosphonate and bisphosphonate naive groups, respectively, the change in spinal BMD was 9.0% and 7.8% (P=0.54) at 12 months and 9.8% and 6.1% (P=0.30) at 18 months. The respective change in hip BMD was 1.0% and -0.3% (P=0.36) at 12 months and 2.8% and 1.3% (P=0.44) at 18 months. There was a trend toward a smaller but still significant increase in P1NP in response to teriparatide in bisphosphonate-treated patients. Although this suggests a blunting of the anabolic effects, in our clinic population this did not result in a reduction in BMD gain.