LB0002 COVID-19 VACCINE SAFETY IN PATIENTS WITH RHEUMATIC AND MUSCULOSKELETAL DISEASE

Abstract

Scientific Abstracts 199 ventilation (to maintain SpO 2 ≥92%) and Cohort 2 patients requiring mechanical ventilation, initiated ≤48 hours before randomization. Here, we report results for Phase 2, Cohort 1: 116 patients with severe COVID-19 pneumonia and hyperinflammation from USA, Brazil, Chile, Peru, and South Africa; rand-omized 1:1:1 to receive a single intravenous administration of mavrilimumab (10 or 6 mg/kg) or placebo. The primary efficacy endpoint was proportion of patients alive and free of mechanical ventilation at Day 29. Secondary end-points included [1] time to 2-point clinical improvement (National Institute of Allergy and Infectious Diseases COVID-19 ordinal scale), [2] time to return to room air, and [3] mortality, all measured through Day 29. The prespecified evidentiary standard was a 2-sided α of 0.2 (not adjusted for multiplicity). Results: Baseline demographics were balanced among the intervention groups; patients were racially diverse (43% non-white), had a mean age of 57 years, and 49% were obese (BMI ≥ 30). All patients received the local standard of care: 96% received corticosteroids (including dexamethasone) and 29% received remdesi-vir. No differences in outcomes were observed between the 10 mg/kg and 6 mg/ kg mavrilimumab arms. Results for these groups are presented together. Mavril-imumab recipients had a reduced requirement for mechanical ventilation and improved survival: at day 29, the proportion of patients alive and free of mechanical ventilation was 12.3 percentage points higher with mavrilimumab (86.7% of patients) than placebo (74.4% of patients) (Primary endpoint; p=0.1224). Mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death through Day 29 (Hazard Ratio (HR) = 0.35; p=0.0175). Day 29 mortality was 12.5 percentage points lower in mavrilimumab recipients (8%) compared to placebo (20.5%) (p=0.0718). Mavrilimumab recipients had a 61% reduction in the risk of death through Day 29 (HR= 0.39; p=0.0726). Adverse events occurred less frequently in mavrilimumab recipients compared to placebo, including secondary infections and thrombotic events (known complications of COVID-19). Thrombotic events occurred only in the placebo arm (5/40 [12.5%]). Conclusion: In a global, diverse population of patients with severe COVID-19 pneumonia and hyperinflammation receiving supplemental oxygen therapy, corti-costeroids, and remdesivir, a single infusion of mavrilimumab reduced progression to mechanical ventilation and improved survival. Results indicate mavrilimumab, a potent inhibitor of GM-CSF signaling, may have added clinical benefit on top of the current standard therapy for COVID-19. Of potential importance is that this treatment strategy is mechanistically independent of the specific virus or viral variant. Background: The consequences of the COVID-19 outbreak are unprecedented and have been felt by everyone around the world, including people with rheumatic and musculoskeletal diseases (RMDs). With the development of vaccines, the future is becoming brighter. Vaccines are a key pillar of public health and have been proven to prevent many serious diseases. However, vaccination also raises questions, especially for patients with inflammatory RMDs and/or treated with drugs that influence their immune system. Objectives: Our aim was to collect safety data among RMD patients receiving COVID-19 vaccines. Methods: The EULAR COVID-19 Vaccination (COVAX) Registry is an observational registry launched on 5 February 2021. Data are entered voluntarily by clinicians or associated healthcare staff; patients are eligible for inclusion if they have an RMD and have been vaccinated against SARS-CoV-2. Descriptive statistics are presented. Results: As of 27 April 2021, 1519 patients were reported to the registry. The majority were female (68%) and above the age of 60 (57%). Mean age was 63 years (SD 16), ranging from 15 to 97 years. A total of 28 countries contributed to the registry, with France (60%) and Italy (13%) as the highest contributors. The majority (91%) had inflammatory RMDs. Inflammatory joint diseases accounted for 51% of cases, connective tissue diseases 19%, vasculitis 16%, other immune mediated inflamma-tory diseases 4%, and non-inflammatory/mechanical RMDs 9%. The most frequent individual diagnoses were rheumatoid arthritis (30%), axial spondyloarthritis (8%), psoriatic arthritis (8%), systemic lupus erythematosus (SLE, 7%) and polymyalgia rheumatica (6%). At the time of vaccination, 45% were taking conventional synthetic DMARDs, 36% biological DMARDs, 31% systemic glucocorticoids, 6% other immu-nosuppressants (azathioprine; mycophenolate; cyclosporine; cyclophosphamide; tac-rolimus), and 3% targeted synthetic DMARDs. The most frequent individual DMARDs were methotrexate (29%), TNF-inhibitors (18%), antimalarials (10%) and rituximab (6%). The vaccines administered were: 78% Pfizer, 16% AstraZeneca, 5% Moderna and 1% other/unknown; 66% of cases received two doses and 34% one dose. Mean time from 1st and 2nd dose to case report was 41 days (SD 26) and 26 days (SD 23), respectively. COVID-19 diagnosis after vaccination was reported in 1% (18/1519) of cases. Mean time from first vaccination until COVID-19 diagnosis was 24 days (SD 17). Disease flares were reported by 5% (73/1375) of patients with inflamma-tory RMDs, with 1.2% (17/1375) classified as severe flares. Mean time from closest vaccination date to inflammatory RMD flare was 5 days (SD 5). The most common flare types were arthritis (35/1375=2.5%), arthralgia (29/1375=2.1%), cutaneous flare (11/1375=0.8%) and increase in fatigue (11/1375=0.8%). Potential vaccine side effects were reported by 31% of patients (467/1519). The majority were typical early adverse events within 7 days of vaccination, namely pain at the site of injection (281/1519=19%), fatigue (171/1519=11%) and headache (103/1519=7%). Organ/sys-tem adverse events were reported by 2% (33/1519) but only 0.1% (2/1519) reported