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Background/Aims When the COVID-19 pandemic began, steps were taken to minimise risk to those vulnerable to severe outcomes. For immunosuppressed patients with rheumatoid arthritis (RA), consideration was given to reducing risk whilst mindful of compromising control of their underlying condition. At Leeds Teaching Hospitals NHS Trust, patients receiving rituximab (RTX) were considered for a reduced dose regimen. A retrospective study, using real-world data, was undertaken to assess the impact of lower doses of RTX on response to treatment. Methods The clinical records of all patients with RA who had received RTX between March 2020 and March 2021 were reviewed. Demographics and previous RTX exposure were recorded. The dose of RTX given during the specified period was noted. Response to treatment was recorded pragmatically by physicians as good, partial or none, based on patient reported VAS for disease activity and swollen and tender joint counts, given the limitations placed on face-to-face patient review due to the pandemic. The time to subsequent RTX treatment and the need for steroid treatment for flares was also studied. Results The number of patients treated with RTX was 282, of whom 89 patients received full dose (1g x 2 infusions), 192 patients received half dose (500mg x 2 infusions). The mean age was 61 years. 77% were female. 9% were RTX-naive, 80% had previously had full dose. Follow-up data were available for 185/192 of the group receiving 1g and 88/89 of the group receiving 2g. Clinical outcomes were as follows for the two groups (1g RTX vs 2g RTX): no response 10.3% vs 9.1%; partial response:34.9% vs 20% %; good response: 54.8% vs 70.9%. The mean length of response was 7.5 months in the patients receiving 1g of RTX compared to 8.6 months in the group receiving 2g of RTX. Similar number of patients required steroid for a flare after receiving Ig of RTX (23.9%) compare to those receiving 2g of RTX (25.8%). Conclusion A majority of patients receiving RTX for RA at either standard or reduced dose reported clinical response. Those receiving lower dose RTX were more likely to report a partial response whilst those receiving full dose were more likely to report a good response. Duration of response and need for steroid therapy for flare of RA between treatments did not significantly differ between groups. Further analysis of factors that may influence clinical response to lower dose RTX is ongoing, which could guide tailored therapy regimens should the need arise again. Disclosure J. McLorinan: None. M. Slade: None. C. Leong: None. J. Baker: None. L. Bailey: None. J. Nam: None. L. Bissell: None. P. Emery: None. S. Dass: None. B. Saleem: None.

Background: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. Methods: We evaluated IMD flares or new disease onset within 28-days of SARS-CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. Findings: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the MRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 ± 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second-dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Atypical rheumatic manifestations included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. Interpretation: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. Funding: none.

AimsThe National Institute for Health and Care Excellence advocated the development of specialist skin cancer multidisciplinary teams (SSMDTs) for the management of higher risk invasive skin cancers in the UK. The interobserver variability in the histopathological assessment of primary cutaneous malignant melanoma (PCMM) is well recognised.MethodsWe evaluated the discordance rates in the assessment of the histopathological criteria of PCMM based on the eighth American Joint Committee on Cancer (AJCC) melanoma staging system and subsequent change in prognosis and management following pathology review by an SSMDT.Results353 cases of PCMM were referred to our SSMDT between April 2015 and May 2016. Cases in which there was a discrepancy in one or more histological parameters following expert review were collected retrospectively. Of 341 eligible cases, there were 94 (27.6%) in which there was an alteration in any parameter. There was interobserver agreement in final diagnosis in 96.8%, Breslow thickness in 86.8%, ulceration in 98.2%, microsatellites in 98.5%, tumour mitotic rate in 88.9%, histological subtype in 92.4%, growth phase in 98.5%, angiolymphatic invasion in 97.7%, perineural invasion in 98.8%, regression in 95.3% and tumour-infiltrating lymphocytes in 95.0%. A corresponding change in AJCC stage occurred in 23 cases (6.7%), with a resulting change in clinical management in 10 cases (2.9%).ConclusionsDisagreements in the pathological assessment of PCMM can have significant clinical implications for a small number of patients. Our findings highlight the value of the SSMDT for high-quality care of patients with melanoma in the UK.