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Summary Background Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behcet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behcet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31–1·57]), were male compared with female (1·38 [1·05–1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23–1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50–3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49–3·02]). Risk factors varied among different disease subtypes. Interpretation Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. Funding American College of Rheumatology and the European Alliance of Associations for Rheumatology.

International audience; Objective. To evaluate the impact of telemedicine use during the coronavirus disease 2019 (COVID-19) pandemic on rheumatology trainees. Methods. A voluntary, anonymous, web-based survey was administered in English, Spanish, or French from August 19 to October 5, 2020. Adult and pediatric rheumatology trainees were invited to participate via social media and email. Using multiple-choice questions and Likert scales, the survey assessed prior and current telemedicine use, impact on training, and supervision after COVID-19 prompted rapid telemedicine implementation. Results. Surveys were received from 302 trainees from 33 countries, with 83% in adult rheumatology training programs. Reported telemedicine use increased from 13% before the pandemic to 82% during the pandemic. United States trainees predominantly used video visits, whereas outside the United States telemedicine was predominantly audio only. Most (65%) evaluated new patients using telemedicine. More respondents were comfortable using telemedicine for follow-up patients (69%) than for new patients (25%). Only 39% of respondents reported receiving telemedicine-focused training, including instruction on software, clinical skills, and billing, whereas more than half of United States trainees (59%) had training. Postconsultation verbal discussion was the most frequent form of supervision; 24% reported no supervision. Trainees found that telemedicine negatively impacted supervision (50%) and the quality of clinical teaching received (70%), with only 9% reporting a positive impact. Conclusions. Despite widespread uptake of telemedicine, a low proportion of trainees received telemedicine training, and many lacked comfort in evaluating patients, particularly new patients. Inadequate supervision and clinical teaching were areas of concern. If telemedicine remains in widespread use, ensuring appropriate trainee supervision and teaching should be prioritized. No funding was received for this study. The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the American College of Rheumatology, the European League Against Rheumatism, or any other organization.

Background: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide. Methods: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis. Findings: 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjogren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514). Interpretation: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity. Funding: American College of Rheumatology.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Fatigue is a common symptom described by people with Sjögren’s syndrome. There are different patterns of fatigue, and people with Sjögren’s syndrome may experience tiredness of a different nature compared to a healthy individual. The aetiology of fatigue is not fully understood and is likely to be multifactorial. There are a number of fatigue outcome measures and disease-activity scores used to assess and monitor fatigue. We discuss pharmacological therapies which have been studied in the context of fatigue and allude to nonpharmacological interventions to address fatigue. We also highlight the importance of incorporating assessment of fatigue due to the significant impact on the quality of life of patients and their abilities to carry out activities of daily living.

Background/Aims COVID-19 poses many challenges to the way in which rheumatology services are delivered. In particular, the sudden change from face-to-face (F2F) appointments to telephone consultations (TC) has adversely impacted upon the assessment and management of disease activity. Therefore, we established a dedicated urgent F2F rheumatology clinic to rapidly assess new or follow-up patients with symptoms that could not be managed remotely during the pandemic. Herein we present patient outcomes to inform future service planning in the context of the ongoing pandemic and continuing need for rationing of F2F services. Methods Patients requiring urgent F2F assessment between 22nd April and 28th July 2020 were evaluated. Referrals came from rheumatologists, rheumatology trainees, nurse specialists, general practitioners, and other medical teams. Prior to attendance, patients were screened for symptoms of COVID-19 by a clinician. Temperature monitoring was performed on the day of attendance. A retrospective review of electronic medical records was conducted in which we identified outcomes of all patients reviewed. Results A total of 201 patients were scheduled an appointment (10 did not attend). Mean age was 45.4±16.6 years of which 14% were ‘shielding’. In all, 85% of patients were referred following a previous TC in which assessment and/or treatment could not be done remotely. New referrals consisted primarily of possible new inflammatory arthritis (55%), new autoimmune rheumatic disease (6%) or polymyalgia rheumatica (4%) with 23% currently undergoing investigation to confirm diagnosis. All patients required physical examination and alteration in investigation and/or management. Of those who attended, blood tests (66%), radiographs (32%), MRI (14%), and ultrasound (8%) were the most common investigations requested. In total 14% were referred to another secondary care specialty, 14% to physiotherapy, and 13% for specialist nurse review. Regarding treatment, 25% required intra-articular joint injection (37 patients received a total of 45 joint injections on the day of the clinic with a further 10 patients referred for ultrasound-guided injection); 13% of patients received intramuscular steroids; and 16% were prescribed oral steroids. New disease-modifying anti-rheumatic drug therapy was initiated in 17% of cases with an additional 11% starting a new biologic agent. No patients had their treatment reduced or discontinued. We are not aware of any new cases of COVID-19 following attendance at this clinic. Conclusion This urgent clinical service was formed because virtual remote consultations alone were insufficient to address the clinical needs of our patients. We found this service to be safe and effective for assessment of patients, with escalation of treatment according to clinical need, in spite of the adverse impact of COVID-19 upon our services. However, for future service planning during the ongoing COVID-19 pandemic this F2F service requires the availability and support of nursing, allied healthcare professionals, pharmacy and diagnostic services. Disclosure C. Wincup: Grants/research support; CW has received funding for research from LUPUS UK, Versus Arthritis, British Society for Rheumatology. R. Amarnani: None. S. Rana: None. J. Tan: None. F. Farinha: Grants/research support; FF has received funding for research from LUPUS UK and the Portuguese Foundation for Science and Technology. S. Yeoh: Grants/research support; SAY has received research funding from (UCLH NIHR BRC), UCLH Charities, Royal College of Physicians, Rosetrees Trust. C. Raine: Grants/research support; CR has received funding for research from UCB. I. Giles: None.

Background/Aims Patient and public involvement (PPI) initiatives are important to ensure patient-centered research. However, traditional focus groups can present challenges including the recruitment and retention of patient partners. Additional challenges to patient involvement have also arisen due to the coronavirus pandemic (COVID-19). The University College London (UCL) Patient Partners in Rheumatology Research initiative has been developed to explore novel ways to boost patient involvement and foster an active collaboration between basic researchers and patient partners. Methods Two online surveys were designed to obtain information with regards to the expectations and practicalities of this initiative. One survey was sent to patients who had registered an interest in being patient partners and the other survey to rheumatology researchers at UCL and University College London Hospital (UCLH). Results We received responses from 25 researchers and 21 patients. The majority of patients who responded (71%) had not previously been involved in PPI. Most of the researchers (84%) had previously utilised PPI, however 20% of those had some difficulty accessing it. Most patients (86%) were interested in becoming a patient partner. Amongst those with reservations, one stated that “I don't think I have the qualifications to be involved with scientists and researchers”. Over half of patients (52%) were happy to participate in PPI more than five times a year and most researchers (84%) expressed that five times a year was acceptable. Patients favoured (52%) conducting PPI meetings after office hours (5-8pm) during the working week. Due to social restrictions because of COVID-19, we asked both patients and researchers their preferred mode of meeting. Both groups favoured a mixed (virtual and face to face) meeting arrangement (81% for patients and 68% for researchers). A third of patients (38%) expressed that they would need technical assistance accessing a virtual meeting. Almost all patients (95%) were happy to contribute to lay summary reviews remotely via email. Conclusion Based on the insights gained from the survey results, our PPI initiative meetings will be hosted in a hybrid virtual/face to face format. These will be held at a time and frequency that is convenient for the patient partners to increase participation across wider demographics. This survey has highlighted that we have to be mindful of certain patient perceptions of PPI which creates a barrier to patient involvement and that some individuals may require further support in accessing virtual meetings. By designing a PPI initiative that creatively addressed the needs of both the researchers and patient partners we hope to create a platform for productive dialogue and collaboration to ensure patient-centred research, despite the changes brought about by the COVID-19 pandemic. Disclosure E. Hawkins: Other; funded by National Institute of Health Research, Clinical Research Network. T. Hyndman: None. R. Amarnani: None. J. Kimpton: None. S. Yeoh: Other; University College London Hospital National Institute of Health Research Biomedical Research Centre, UCLH Charities, Royal College of Physicians and Rosetrees Trust. M. Castelino: Other; University College London Hospitals National Institute for Health Research Biomedical Research Centre.

Background/Aims Rheumatologists are facing a significant challenge in the management of early rheumatoid arthritis (RA) due to limitations placed on outpatient visits during the COVID-19 pandemic. Frequent clinical assessments of disease activity are recommended during implementation of the treat to target strategy to achieve remission. A biomarker indicating response to methotrexate during the early phase of therapy could complement clinical examination. Methotrexate increases erythrocyte mean corpuscular volume (MCV), which is measured routinely, prompting us to investigate whether changes in MCV could act as an early indicator of response. Methods Patients with early RA who were started on methotrexate therapy were included from two independent cohorts. The larger cohort (discovery cohort, n = 655) was used to build the model and the second cohort (validation cohort, n = 225) was applied to test the prediction of the model. Conventional statistical, and machine learning approaches were adopted to identify key determinants that influence the potential relationship between MCV and clinical response, defined as attainment of remission or low disease activity, at six months after starting methotrexate. Results A LASSO penalised logistic regression model was built with the discovery cohort [area under the receiver operating characteristics (AUROC) curve = 0.76], where change of MCV from three months [Odds ratio (OR) 1.53 (95% CI 1.38-1.70)], concomitant use of hydroxychloroquine [OR 2.16 (95% CI 1.52 - 3.07, p < 0.001)], and seropositivity [OR 1.83 (95% CI 1.12 - 3.03, p = 0.02)] were associated with favourable methotrexate response [accuracy 81% (95% CI 76%-86%) of the model testing against discovery model]. Different machine learning classification methods were applied. Random forest exhibited the maximum accuracy and AUROC (89%, and 86%, respectively), confirming the above three predictors as the most significant. Two latent classes (class 1: smaller MCV increase and class 2: greater MCV increase) were identified based on the MCV changes over six months. Class 1 had fewer responders and a lower number of patients on hydroxychloroquine compared to class 2. The earliest time point of significant difference of MCV between responders and non-responders was three months [mean difference 1.43 (95% CI 0.57-2.3)]. Combination hydroxychloroquine and methotrexate caused the greatest increase in MCV with a difference between responders and non-responders at 2 months. Change of MCV at three months showed AUROC of 0.75 to predict treatment response to the combination of methotrexate and hydroxychloroquine at six months with an optimal cut-point of MCV 3.5 fL (95% CI 3.5-3.6) with 71% sensitivity and 75%, specificity. Conclusion Our data provides mechanistic insight into the synergistic clinical benefit of concomitant hydroxychloroquine with methotrexate, boosting the rise in erythrocyte MCV which could serve as an early biomarker of treatment response. Disclosure M.R. Shipa: Grants/research support; Versus arthritis. S. Yeoh: Grants/research support; Royal College of Physicians, Rosetrees Trust, NIHR University College London Hospitals Biomedical Research Centre, UCLH Charities. A. Embleton-Thirsk: None. D. Mukerjee: None. M.R. Ehrenstein: Grants/research support; University College London Hospital Biomedical Research Centre.

Pulmonary manifestations of systemic lupus erythematosus (SLE) are wide-ranging and debilitating in nature. Previous studies suggest that anywhere between 20 and 90% of patients with SLE will be troubled by some form of respiratory involvement throughout the course of their disease. This can include disorders of the lung parenchyma (such as interstitial lung disease and acute pneumonitis), pleura (resulting in pleurisy and pleural effusion), and pulmonary vasculature [including pulmonary arterial hypertension (PAH), pulmonary embolic disease, and pulmonary vasculitis], whilst shrinking lung syndrome is a rare complication of the disease. Furthermore, the risks of respiratory infection (which often mimic acute pulmonary manifestations of SLE) are increased by the immunosuppressive treatment that is routinely used in the management of lupus. Although these conditions commonly present with a combination of dyspnea, cough and chest pain, it is important to consider that some patients may be asymptomatic with the only suggestion of the respiratory disorder being found incidentally on thoracic imaging or pulmonary function tests. Treatment decisions are often based upon evidence from case reports or small cases series given the paucity of clinical trial data specifically focused on pulmonary manifestations of SLE. Many therapeutic options are often initiated based on studies in severe manifestations of SLE affecting other organ systems or from experience drawn from the use of these therapeutics in the pulmonary manifestations of other systemic autoimmune rheumatic diseases. In this review, we describe the key features of the pulmonary manifestations of SLE and approaches to investigation and management in clinical practice.

Maintenance of remission once achieved is becoming a critical goal for patients with rheumatoid arthritis (RA) as outcomes improve and advances in therapies continue.1 2 Identification of biomarkers to facilitate tailoring of treatment is often linked to modest response criteria, but less frequently to the more stringent target of sustained remission. We have previously implicated monocytes as potential predictor of response to anti-tumour necrosis factor (TNF) through modulation of regulatory T cells, which may promote maintenance of remission through re-establishment of immune tolerance.3 Circulating monocyte numbers are increased in RA but fall in patients who respond to TNF blockade.4 Whether changes in monocyte numbers can also predict loss of remission, once achieved, to anti-TNF therapy is unknown. We therefore addressed whether the change in monocyte counts in the first year from initiation of anti-TNF therapy (baseline) would predict loss of remission (LOR) in patients who achieved sustained remission. We extracted data (June 2020) from two independent cohorts of adult biologic-naive patients with RA who attained sustained remission while treated with anti-TNF between January 2008 and December 2019 (online supplemental table 1). In this retrospective study, Disease Activity Score-28 (DAS28) with erythrocyte sedimentation rate ≤2.6 on at least two occasions (3–6 months apart) after initiation of anti-TNF therapy was used as the definition of remission, as this index was routinely calculated at the treating hospitals. A more stringent definition of remission based on the Clinical Disease Activity Index (CDAI ≤2.8) …

Background Immune-mediated necrotising myopathy (IMNM) is characterised by severe muscle weakness and necrosis with a paucity of inflammation on muscle biopsy. Around 60% of cases are associated with antibodies to the signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR); the remainder are seronegative. IMNM is more treatment resistant than inflammatory myopathies. Case presentation A 69-year-old woman with previous statin exposure presented aged 63 with muscle weakness and raised creatinine kinase (CK). Anti-SRP and anti-HMGCR antibodies were not detected, but muscle biopsy revealed changes consistent with necrotising myopathy. Statins were discontinued, and she was treated with prednisolone and methotrexate achieving disease remission. Clinical and biochemical parameters were largely stable until 6 years after diagnosis she experienced a rapid deterioration. This was found to be associated with new development of anti-HMGCR antibody. Rituximab was commenced, resulting rapidly in remission. She has remained in remission since, following 2 cycles of rituximab. Conclusions To our knowledge, this is the first reported case of serologically negative IMNM whose subsequent rapid deterioration was associated with development of anti-HMGCR antibody. The response to rituximab and subsequent sustained remission suggests a role for early use of rituximab in aggressive cases of anti-HMGCR myopathy.

The benefits of coprescribing methotrexate (MTX) with tumour necrosis factor (TNF)-inhibitors are well documented in rheumatoid arthritis (RA), though rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) status have not always been taken into account.1 Increasing doubt about the value of combination MTX and anti-TNF therapy in psoriatic arthritis2 3 led us to evaluate whether MTX reduced withdrawal rates due to ineffectiveness of anti-TNF therapy equally in seropositive and seronegative RA. Treatment durations for adalimumab or etanercept were analysed for 301 patients with RA using retrospective, real-world data from a single centre. All had started adalimumab or etanercept as a first-line biologic from 2003 onwards. Rates of ineffectiveness-related withdrawal during the first 5 years of anti-TNF therapy were analysed using Kaplan-Meier and Cox regression, with comparison of rates with respect to concomitant MTX at anti-TNF initiation. Fifty-two withdrawals for adverse events and 10 for other reasons constituted censored cases as did 136 still on anti-TNF at 5 years and 60 …

Background A 32-year-old Lithuanian lady, with a 6-year history of undifferentiated inflammatory arthritis and autoimmune neutropenia, contacted her rheumatologist reporting a constellation of new symptoms. This began with a month’s history of facial weakness and slurred speech. She progressively experienced nasal regurgitation on drinking fluids, reduced exercise tolerance, as well as difficulty chewing, swallowing, and coughing. Her symptoms initially came on in the evening but subsequently appeared earlier in the day. There were no symptoms suggestive of infection. Her arthritis had been well-controlled on hydroxychloroquine and sulfasalazine. She was previously on methotrexate, but this was discontinued due to plans to conceive. Methods Clinical examination during an urgent outpatient review yielded dysphonic, mildly dysarthric speech. Extraocular movements were normal with no ophthalmoplegia. There was mild lower motor neurone facial weakness and an absent gag reflex. She demonstrated fatiguability on repetitive tongue movements and arm abduction. There were no upper motor neurone or cerebellar signs. Blood tests showed normal inflammatory markers, full blood count, creatine kinase, immunoglobulins, liver, and renal profile. Her anti-nuclear antibody titre, previously weakly positive at time of diagnosis of inflammatory arthritis, was 1:1280 (homogenous). Anti-cyclic citrullinated peptide, rheumatoid factor, and extractable nuclear antigens were negative. Virology screen was unremarkable. Neurology input was sought. Anti-acetylcholine receptor antibody was positive at 5.2nmol/L (normal range 0-0.45nmol/L), anti-muscle specific receptor tyrosine kinase antibody was negative. Nerve conduction studies showed decremental response on repetitive stimulation of her left nasalis, consistent with a post-synaptic neuromuscular junction transmission disorder. There was no evidence of myopathy. Results The clinical symptoms and the investigations led to the diagnosis of myasthenia gravis with predominant bulbar features. Computed tomography showed no evidence of thymoma or thymic hyperplasia. Magnetic resonance imaging of the brain showed no evidence of space-occupying lesion or brainstem abnormality. She initially received pyridostigmine 30mg three times daily with propantheline cover to which she reported a good response. A viral illness led to deterioration of her symptoms of breathlessness and worsening dysphagia resulting in a hospital admission. She received intravenous immunoglobulins 20g daily for three days. Hydroxychloroquine and sulfasalazine were replaced with methotrexate 15mg weekly. She now remains on pyridostigmine 90mg five times daily and 10mg prednisolone daily with good effect. Conclusion Myasthenia gravis is a rare condition (prevalence of 10-20 per 100,000 in the United Kingdom). However, this occurs at a higher prevalence in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. This case illustrates the importance of remaining vigilant about symptoms which patients may disclose in the rheumatology clinic which may not fit with their known diagnosis. Her previous use of methotrexate for her arthritis could have masked her myasthenic symptoms which became apparent after the drug was stopped for a prolonged period. Disclosures S. Yeoh None. S. Salam None. G. Christofi None. V. Morris None.

Background:Abatacept, a selective inhibitor of T cell co-stimulation, is often used as a second-line biologic disease-modifying anti-rheumatic drug (bDMARD) after the failure of tumour necrosis factor inhibitor (TNFi) in Rheumatoid Arthritis (RA). However, in comparison to TNFi very few survival analyses of abatacept have been reported.1,2Objectives:To investigate predictors of abatacept discontinuation due to either inefficacy or adverse events in RA patients over 5-years.Methods:A retrospective observational analysis was conducted on a tertiary hospital dataset of RA (according to 2010 ACR/EULAR criteria) patients who started abatacept (either intravenous or subcutaneous). Time to abatacept discontinuation over 5-years was estimated using Kaplan-Meier survival analyses. A multivariate cox-regression model to predict abatacept discontinuation was chosen by elastic net regularisation.Results:A total of 112 patients with RA [81% female, mean age 58.1 (SD 13.5) years] commenced abatacept therapy during the study period. 88 (78.6%) patients received intravenous abatacept, 14 (15.9%) of whom switched to subcutaneous injection, and 24 (21.4%) were initially treated with subcutaneous abatacept, 2 (8.3%) of whom switched to intravenous. More than half of the patients (65/112) were treated with at least one concomitant conventional synthetic DMARD (csDMARD). Methotrexate was the most commonly used (n = 37) csDMARD, followed by hydroxychloroquine (n = 23), sulfasalazine (n= 15), and leflunomide (n = 7). 42 (37.5%) patients were treated with glucocorticoids (either oral, intra-articular, or intramuscular injection) during the time they were treated with abatacept. Abatacept was most commonly used as 4th (n = 29) and 3rd line (n = 24) bDMARD but 19 patients received abatacept as their first line bDMARD. 75 (67%) patients were rheumatoid factor (RF) positive and 73 (65.2%) were anti-citrullinated protein antibody (ACPA) positive. Anti-nuclear antibody (ANA) was positive in 32 patients. Abatacept was discontinued in 54 patients (48.2%); 19 (35.2%) due to an adverse event and 35 (64.8%) due to loss of efficacy. Overall, the median time to discontinuation of abatacept was 3.8 years.Multivariate cox regression (variables chosen by the elastic net and adjusted by whether or not abatacept was used as first-line therapy) showed that ACPA positivity was associated with a reduced risk of abatacept discontinuation with a hazard ratio (HR) of 0.40 (95% CI 0.18 to 0.85, p=0.02, N. of events 16/47) compared to ACPA negative patients (N. of events 15/23), but only if ANA was negative. In contrast, ACPA positivity did not reveal any retention benefit over ACPA negative patients, if they were ANA positive.ACPA positive patients without positive ANA increased the time-to-discontinuation of abatacept predominantly after 3-months (unadjusted log-rank p=0.02), compared to ACPA, and ANA negative patients (Figure 1). Adding csDMARDs with abatacept, reduced the risk of discontinuation of abatacept by 59% (95% CI 24% to 77%, p = 0.004, N. of events 26/65) compared to monotherapy (N. of events 28/47).Conclusion:Our data suggests patients who are ACPA positive and ANA negative are more likely to remain on abatacept therapy. Concomitant csDMARD use also acts as a positive predictor of abatacept treatment retention.References:[1]Cagnotto G, et al. Arthritis Res Ther. 2020;22(1):15.[2]Alten R, et al. Clin Rheumatol. 2019;38(5):1413-1424.Figure 1.Kaplan-Meier survival curve of retention of abatacept, stratified by Anti-citrullinated protein antibody (ACPA) and antinuclear antibody (ANA).+ACPA/-ANA = ACPA positive and ANA negative, +ACPA/+ANA = ACPA positive and ANA positive, -ACPA/-ANA = ACPA negative and ANA negative, -ACPA/+ANA = ACPA negative and ANA positive, HR = Hazard ratio.Acknowledgements:I have no acknowledgements to declare.Disclosure of Interests:None declared

Background:The COVID-19 pandemic has disrupted healthcare delivery and education of physicians, including rheumatology trainees.Objectives:To assess the impact of the COVID-19 pandemic on the clinical experiences, research opportunities, and well-being of rheumatology trainees.Methods:A voluntary, anonymous, web-based survey was administered in English, Spanish, or French from 19/08/2020 to 05/10/2020. Adult and paediatric rheumatology trainees worldwide in training in 2020 were invited to participate via social media and email. Using multiple choice questions, Likert scales, and free text answers, we assessed trainee patient care activities, redeployment, research, and well-being.Results:The 302 respondents were from 33 countries, with most (83%, 252/302) in adult rheumatology training. Many trainees (45%, 135/300) reported an increase in non-rheumatology clinical work (e.g. care of COVID-19 patients), with 52% of these (70/135) also continuing rheumatology clinical work. COVID-19 redeployment was not optional for 68% (91/134).Trainees reported a negative impact of the pandemic in their growth in rheumatology (Figure 1). They also reported a substantial impact on several training areas: outpatient clinics (79%, 238/302), inpatient consultations (59%, 177/302), formal teaching (55%, 167/302), procedures (53%, 147/302), teaching opportunities (52%, 157/302), and ultrasonography (36%, 110/302), with 87-96% perceiving a negative impact on these areas. Only 54% (159/294) reported feeling comfortable with their level of clinical supervision during the pandemic (Figure 1).Many trainees (46%, 128/280) reported changes in research experiences during the pandemic; 39% (110/285) reported that COVID-19 negatively affected their ability to continue their pre-pandemic research and 50% (142/285) reported difficulty maintaining research goals (Figure 1).Some rheumatology trainees reported having health condition(s) putting them at high risk for COVID-19 (10%, 30/302) and 14% of trainees (41/302) reported having had COVID-19 (Table 1). Only 53% (160/302) reported feeling physically safe in the workplace while 25% (76/302) reported not feeling physically safe; reasons included lack of training about COVID-19, lack of comfort in the clinical setting, insufficient personal protective equipment, immunocompromised state, and pregnancy. Half (151/302) reported burnout and 68% (204/302) an increase in stress from work during the pandemic (Figure 1), whilst 25% (75/302) reported that changes to their training programme negatively impacted their physical health.Conclusion:The COVID-19 pandemic has negatively impacted the experience of rheumatology training as well as the well-being of trainees globally. Our data highlight concerns for rheumatology trainees including research opportunities and clinical care which should be a focus for curriculum planning.Figure 1.Rheumatology trainee perceptions of pandemic impact and changes in training programme.Table 1.Estimated hazard ratios, adjusted for age and gender, for individuals with rheumatoid arthritisEuropen = 89ROWn = 213Combinedn = 302Disability1 (1)9 (4)10 (3)High risk7 (8)23 (11)30 (10)Pregnant4 (5)15 (7)19 (6)Shielding/Quarantining12 (13)70 (33)82 (27)Acquired COVID-1920 (22)21 (10)41 (14)Disclosure of Interests:Kristen Young: None declared, Su-Ann Yeoh: None declared, Michael Putman: None declared, Elizabeth Graef: None declared, Francis Berenbaum: None declared, Richard Conway: None declared, Rebecca Grainger Speakers bureau: Speaker fees from Abbvie, Janssen, Novartis, Pfizer, Cornerstones, all not related to this work, Consultant of: Consultancy fees from Abbvie, Janssen, Novartis, Pfizer, Cornerstones, all not related to this work, Grant/research support from: Travel assistance from Pfizer, not related to this work, Adam Kilian: None declared, Maximilian Konig: None declared, Jean Liew Grant/research support from: Research grant from Pfizer unrelated to this manuscript, Pedro M Machado Speakers bureau: Speaker fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Consultant of: Consulting fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Sebastian E. Sattui: None declared, Jeffrey Sparks Consultant of: Consultancy for Bristol-Myers Squibb, Gilead, Inova Diagnostics, Optum, and Pfizer unrelated to this manuscript, Grant/research support from: Research support from Bristol-Myers Squibb unrelated to this manuscript, Paul Sufka: None declared, Manuel Ugarte-Gil Grant/research support from: Research grants from Janssen and Pfizer unrelated to this manuscript, Laura Upton: None declared, Zachary Wallace: None declared, Jinoos Yazdany Consultant of: Consultancy for Astra Zeneca, Eli Lilly, and Pfizer, not related to this work, Grant/research support from: Research grants from Gilead and Pfizer, not related to this work, Arundathi Jayatilleke: None declared.

Background:The COVID-19 pandemic led to a rapid increase in remote consultations in rheumatology care. Due to the potential impact of this change on rheumatology clinical training, we investigated trainees’ experiences with telemedicine.Objectives:To assess the impact of telemedicine use during the COVID-19 pandemic on rheumatology training, including supervision.Methods:A voluntary, anonymous web-based survey was administered in English, Spanish, or French from 19/08/2020 to 05/10/2020. Adult and paediatric rheumatology trainees worldwide in training in 2020 were invited to participate via social media and email. Using multiple choice questions, Likert scales, and free text answers, we collected data regarding prior and current telemedicine use, training, and supervision.Results:302 respondents from 33 countries completed the survey, with most (83%, 252/302) in adult rheumatology training. Reported use of telemedicine increased from 13% (39/302) pre-pandemic to 82% (247/302) (Table 1). European trainees predominantly utilised audio-only compared to trainees from the rest of the world (ROW) who predominantly utilised audio-video telemedicine.Most trainees continued to evaluate new patients using telemedicine (65%, 161/247). A larger proportion of trainees were comfortable using telemedicine to evaluate follow-up (69% 170/247) versus new patients (25%, 41/161) (Figure 1).Only 32% (97/302) were trained in telemedicine, with the highest proportion among United States (US) trainees (59%, 69/116); subjects included software, clinical skills, and billing. The majority of trainees found this helpful (92%, 89/97).Supervision was most frequently in the form of verbal discussion after the consultation (Table 1); 24% (59/247) had no telemedicine supervision during the pandemic. In general, trainees found telemedicine negatively impacted their supervision (51%, 123/242) and clinical teaching quality (70%, 171/244); only 9% reported a positive impact on these areas.Conclusion:Adoption of telemedicine during the COVID-19 pandemic has led to areas of concern for rheumatology trainees including inadequate supervision and clinical teaching. Our results suggest a need for education on evaluation of new patients using telemedicine, increasing telemedicine training, and ensuring adequate supervisory arrangements.Table 1.Telemedicine use, supervision, and training by region. Data is presented as n (%). Rest of the world (ROW) data includes Asia (50), Central and South America (23), Canada (12), Australia (8), and Africa (4).Europen = 89USn = 116ROWn = 97Combinedn = 302Telemedicine usePre-pandemic15 (17)9 (8)15 (15)39 (13)During pandemic64 (72)112 (97)71 (73)247 (82)Telemedicine modalitypre-pandemicAudio-only14 (93)3 (33)8 (53)25 (64)Audio-video1 (7)7 (78)7 (47)15 (38)Telemedicine modality during pandemicAudio-only56 (88)47 (42)51 (72)154 (62)Audio-video7 (11)100 (89)29 (41)136 (55)Supervisionpre-pandemicReal-time observation (part of visit)0 (0)4 (44)3 (20)7 (18)Real-time observation (full visit)0 (0)2 (22)2 (13)4 (10)Verbal discussion after8 (53)3 (33)7 (47)18 (46)Written communication after0 (0)0 (0)1 (7)1 (3)None7 (47)2 (22)5 (33)14 (36)Supervision during pandemicReal-time observation (part of visit)2 (3)54 (48)15 (21)71 (29)Real-time observation (full visit)3 (5)32 (29)8 (11)43 (17)Verbal discussion after32 (50)65 (58)28 (39)125 (51)Written communication after7 (11)15 (13)9 (13)31 (13)None28 (44)9 (8)22 (31)59 (24)Figure 1.Rheumatology trainee comfort levels in using telemedicine during the pandemic.Disclosure of Interests:Su-Ann Yeoh: None declared, Kristen Young: None declared, Michael Putman: None declared, Elizabeth Graef: None declared, Francis Berenbaum: None declared, Richard Conway: None declared, Rebecca Grainger Speakers bureau: Speaker fees from Abbvie, Janssen, Novartis, Pfizer, Cornerstones, all not related to this work, Consultant of: Consultancy fees from Abbvie, Janssen, Novartis, Pfizer, Cornerstones, all not related to this work, Grant/research support from: Travel assistance from Pfizer, not related to this work, Adam Kilian: None declared, Maximilian Konig: None declared, Jean Liew Grant/research support from: Research grant from Pfizer unrelated to this manuscript, Pedro M Machado Speakers bureau: Speaker fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Consultant of: Consulting fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Sebastian E. Sattui: None declared, Jeffrey Sparks Consultant of: Consultancy for Bristol-Myers Squibb, Gilead, Inova Diagnostics, Optum, and Pfizer unrelated to this manuscript, Grant/research support from: Research support from Bristol-Myers Squibb unrelated to this manuscript, Paul Sufka: None declared, Manuel Ugarte-Gil Grant/research support from: Research grants from Janssen and Pfizer unrelated to this manuscript, Laura Upton: None declared, Zachary Wallace: None declared, Jinoos Yazdany Consultant of: Consultancy for Astra Zeneca, Eli Lilly, and Pfizer, not related to this work, Grant/research support from: Research grants from Gilead and Pfizer, not related to this work, Arundathi Jayatilleke: None declared

Background:Sustained remission is the ultimate goal in the management of rheumatoid arthritis (RA) but is infrequently achieved. After conventional therapy, TNFi (tumour necrosis factor inhibitor) has a strong track record for achieving remission. Existing studies suggest variable effect of RA and TNFi on various cellular components of the full blood count (FBC), but their relationship with loss of remission (LOR) is unclear.Objectives:To investigate whether cellular changes in the FBC can predict LOR (remission defined as DAS28-ESR≤2.6) in patients with RA receiving TNFi, adjusted using key clinical factors.Methods:Real-world clinical and routine laboratory data were analysed from two independent cohorts of adult RA patients, who were started on their first TNFi (from 2009 to December 2019), and went into remission. Data was extracted in October 2020. A linear mixed model was used to investigate longitudinal changes of different components of FBC and CRP, stratified by LOR, and grouped by years of follow-up. Pairwise post-hoc comparisons were performed by Bonferroni correction. Area Under the Receiver Operating Characteristics (AUROC) of cellular changes in FBC components to predict LOR at different time points were calculated. Latent class mixed models were used to investigate trajectories of change in cellular components of the FBC from baseline to one year. Further survival analysis to predict LOR of TNFi was done by using the latent class model and adjusted by clinical parameters, demographics and concomitant treatment.Results:92 and 43 biologic-naïve RA patients who attained remission were included from cohorts 1 and 2 respectively. 73 (54%) were treated with adalimumab and 62 (46%) with etanercept. 87 (64%) of patients lost remission over a 10-year period with median time to LOR of 3.3 years (95% CI 2.6-3.7).Among the cellular components of FBC, monocyte count changes in the first year after initiation of TNFi fell significantly in those who maintained remission over the five years of follow-up, compared to those who lost remission [pp=0.001) compared to the other 2 classes. Monocyte latent classes as a predictor of LOR was further tested by cox-regression, where variables (anti-citrullinated protein antibody/ACPA, concomitant methotrexate, baseline DAS28-ESR) were selected by elastic net regularisation and further adjusted by use of steroid, age and gender. Class 2 and Class 3 monocyte latent classes showed a hazard ratio (HR) of 3.15 (95% CI 1.02-9.74, p = 0.046, n. of event = 6/7) and 5.48 (95% CI 2.6-11.57, p p = 0.04 (n. of event = 78/117) compared to seronegative patients (n. of event = 9/18).Conclusion:In seropositive RA patients treated with TNFi, a reduction of total monocyte count in the first year was associated with maintenance of remission in subsequent years. Further studies are required to determine whether these effects are specific to TNFi or reflect sustained remission in RA irrespective of therapy.Figure 1(A-F). Mean change (with 95% confidence interval) in absolute count of monocyte after initiation of tumour necrosis factor inhibitor grouped by years of follow-up and stratified by loss of remission. N = number indicate cumulative number of patients who lost remission by the end of each year.Acknowledgements:Muhammad Shipa is funded by Versus Arthritis. Su-Ann Yeoh is funded by the Royal College of Physicians, Rosetrees Trust, NIHR University College London Hospitals Biomedical Research Centre, UCLH Charities, and Versus Arthritis. Michael Ehrenstein is supported (in part) by the University College London Hospital Biomedical Research Centre. None of the funding bodies have been involved in preparation of this manuscript.Disclosure of Interests:None declared

Background:The patent for adalimumab originator expired in 2018 in the United Kingdom. Subsequently, four adalimumab biosimilars were launched. National Health Service England undertook a managed market share tender to ensure plurality of suppliers and price competition over the longer term. Each hospital was subsequently allocated a preferred brand of adalimumab biosimilar. Here we describe our experience of switching patients with inflammatory arthritis from adalimumab originator to the biosimilar, ABP 501 in a single centre.Objectives:To evaluate the proportion of patients successfully switched from adalimumab originator to ABP 501 focusing on drug retention, reasons for remaining on originator and reasons for switching back from biosimilar to originator.Methods:A retrospective analysis was completed on the cohort of 287 rheumatology patients who were prescribed adalimumab originator prior to the switch to ABP 501. Case notes were analysed to identify whether patients remained on biosimilar 24 weeks after switching from originator.Results:99% patients on adalimumab originator (283/287) were switched to ABP 501 within 32 weeks, starting from February 2019. 1% (4/287) remained on originator due to a confirmed latex allergy, as the needle cover of the ABP 501 pre-filled syringe consists of dry natural rubber. 4% (12/283) of patients who switched to biosimilar reverted to originator (1 patient per 2 weeks over 24 weeks). 3% (9/283) of patients who switched to biosimilar were no longer receiving any adalimumab therapy. Reasons for ceasing therapy included recurrent infections (4/9) and progression to the next line of biologics/small molecule therapy (5/9). 93% (262/283) remained stable on ABP 501 (Table). Applications to revert to originator were reviewed by a Biosimilar Steering Group (BSG). The BSG assessment included a review of disease activity, reported symptoms and adverse reactions before and after the switch to biosimilar. Approval to revert to originator occurred in patients who had a clear increase in disease activity or newly reported adverse reactions. If the patient had active disease prior to switch, a change to non-adalimumab therapy would be recommended instead. Of the 12 patients who reverted to originator, 7 (58%) did so due to reduced effectiveness, 3 (25%) due to adverse reactions, and 2 (17%) due to both. Adverse reactions reported within 24 hours of the first injection included nausea, anxiety, insomnia, tinnitus, dizziness, headaches and injection-site reactions. Patients also reported hair loss, fatigue and mouth ulcers. Reported adverse reactions ceased once biosimilar was stopped and/or switching back to originator. All patients who reverted to originator due to reduced effectiveness reported a reduction in disease activity and improvement in symptoms.Conclusion:The vast majority of patients in our cohort on adalimumab were successfully switched from originator to ABP 501. The adalimumab biosimilar has been generally well-tolerated. 93% remained on biosimilar 24 weeks after switching, 4% have switched back to originator and 3% have either stopped or changed treatment. Reasons for switching back to originator from biosimilar included adverse reactions, most of which occurred within 24 hours, and also worsening of symptoms.Table 1.The dynamics of the disease activity during treatment with TOFABaseline characteristics/outcomeTotalN = 283RAN = 90 (32%)SpAN = 108 (38%)PsAN = 77(27%)OtherN = 8(3%)Mean age (SD)49.8 (14.6)58.5 (14.9)43.6 (11.0)48.4 (13.2)46.1 (15.2)Female, n (%)126 (45)67 (74)29 (38)26 (34)4 (50)Reverted to Originatorn (% of patients within subgroup)12 (4)4 (4)6 (6)1 (1)1 (13)Reasons for switching back to OriginatorInefficacy71411Adverse reactions32100Both21100Switched to another biologic agentn (% of patients within subgroup)5 (2)3 (3)2 (2)0 (0)0 (0)Stopped biologicsn (% of patients within subgroup)4 (1)1 (1)1 (1)2 (3)0 (0)Disclosure of Interests:None declared

The majority of rheumatic diseases are chronic and require long-term use of disease-modifying agents to confer the best chance of controlling the disease. A significant proportion of these drugs have a risk, albeit small, of potentially serious side effects, such as neutropenia; therefore, there has been an understandable concern over the use of potentially toxic rheumatic drugs in the elderly. Factors that may contribute to this concern include age, pre-existing co-morbidities, polypharmacy, difficulty in monitoring side effects, and patient perception. The risk of using such medication needs to be balanced with their benefits in controlling chronic disease. This review discusses how rheumatic disease and anti-rheumatic medication are associated with neutropenia in an older age group. Of the rheumatic diseases, we give special focus to rheumatoid arthritis and the use of methotrexate, as well as touching on management considerations in neutropenia.

A 27-year-old female patient from a psychiatric unit presented with a two-week history of abdominal pain and worsening nausea. She admitted to swallowing a ballpoint pen five months prior. Endoscopy showed the tip of the pen impacted in the superior wall of the first part of the duodenum. The endoscopist elected not to retrieve the foreign object and a computed tomograph (CT) was organised. This showed migration of the pen into the liver with the tip in close proximity to the portal vein. Laparoscopic surgery was performed to remove the pen with minimal blood loss. The patient was discharged 12 days later. This case highlights the presence of guidelines to aid decision-making in retrieval of ingested foreign bodies and the value of additional imaging to guide management of foreign body ingestions.