ABSTRACT
Background/AimsLeflunomide, a conventional disease modifying drug (csDMARD), isused in a variety of autoimmune rheumatic diseases (ARD) due to itsimmunomodulating, immunosuppressive and antiproliferative properties. This agent does however confer a greater infection risk and, dueto its long half-life, drug washout procedures are often advised in thecontext of serious infections. Interestingly, Leflunomide is currentlybeing tested as a potential therapy for COVID-19 in the generalpopulation. It is unknown whether leflunomide therapy is associatedwith a poor or favourable outcome among ARD patients infected withCOVID-19.MethodsA Scottish-wide registry was rapidly developed in March 2020. Clinicalcharacteristics and outcomes of infected cases were collated acrossall Scottish health boards. Eligible patients included any adultleflunomide treated ARD patients with a confirmed (clinically or PCR)diagnosis of COVID-19.ResultsOf the 69 cases included in the registry, n = 4 were treated withleflunomide (75% female;mean age 61, SD 4.2). N = 2 were treatedwith combination baricitinib or hydroxychloroquine respectively, whilstn = 1 received recent corticosteroid therapy (intramuscular Kenalog).Comorbidities observed in this sub-cohort include diabetes mellitusn = 3, hypertension n = 2, cardiovascular disease n = 1, lung diseasen = 1 and latent TB n = 1. At presentation, all patients (n = 4)experienced the established COVID-19 related symptom triad ofdyspnoea, cough and fever and promptly developed acute respiratorysyndrome. Diarrhoea was also recorded in n = 2 and constitutionalupset n = 3. All patients suffered a serious COVID-19 disease outcome(defined as a requirement of invasive or non-invasive ventilation (n = 4)and/ or death (n = 2).ConclusionPreliminary data from this Scotland-wide registry has identified only asmall number of leflunomide treated ARD patients infected withCOVID-19. However, it is concerning that all cases experienced aserious outcome. Given the relatively infrequent prescription of thisdrug, combining similar national registry data is necessary to ensurethis observation is not spurious. If confirmed, leflunomide washoutprocedures should be encouraged among such patients when theyfirst present with COVID-19.
ABSTRACT
Background/AimsThe novel infectious disease COVID-19 is associated with a widespectrum of clinical severity amongst the general population. Patientswith autoimmune rheumatic diseases (ARD) are more likely toexperience serious COVID-19 related events, although risk factorsfor such outcomes have yet to be established. In particular, the riskprofiles of specific ARD therapies are unknown.MethodsA Scottish wide registry was rapidly developed in March 2020. Clinicalcharacteristics and outcomes of infected cases were collated acrossall Scottish health boards, leveraging the Scottish Systemic VasculitisNetwork and Scottish Society for Rheumatology. Eligible patientsincluded any adult ARD patients with a confirmed (clinically or PCR)diagnosis of COVID-19. Simple descriptive statistics were employed toevaluate associations between ARD therapies and a serious COVID-19disease outcome, as defined by a requirement of invasive or noninvasive ventilation, and/or death.ResultsA total of 69 patients (59% female;mean age 65.6, SD15.5) wererecruited to the registry , 92% of which required hospitalisation. Caseswere most commonly diagnosed with rheumatoid arthritis (n = 32, 46.4%) followed by spondyloarthritis (n = 19, 27.5%) and systemicvasculitis (n = 9, 13.0%). Anti-TNF therapy (n = 8, 11.6%) andmethotrexate (n = 31, 44.9%) were the commonest biologic andconventional disease modifying drug (bDMARD and csDMARD) usedrespectively. N = 20 (29%) received background corticosteroid therapy (15.9% prednisolone >5mg, 13% prednisolone 5mg). A severeoutcome was observed in n = 25(31.9%);n = 11 required assistedventilation and n = 19 died. With the exception of Leflunomide, conventional and biologic DMARDs did not appear to confer ahigher risk for severe outcome (table 1). Of note, anti-TNF therapywas associated with a non-serious outcome (p = 0.04) and prednisolone>5mg with a serious outcome (p = 0.08). ConclusionPreliminary data from this Scotland-wide ARD COVID-19 registryevidences variation in the impact of standard ARD therapies on theseverity of COVID-19 outcome. In general, background csDMARD andbDMARD use does not appear to be a risk factor for severe outcomes.However, anti-TNF therapy may confer a favourable outcome, whileleflunomide and corticosteroids may have the opposite effect.Rheumatologists should be aware of these possible risk factors andcontinue to contribute to registries to help establish whether theseputative signals are clinically relevant.