Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

No abstract

BackgroundPrimary large vessel vasculitides encompass giant cell arteritis and Takayasu's arteritis. The mainstay of treatment is glucocorticoids, with immuno-suppressants such as methotrexate and azathioprine being used as steroid-sparing agents (1). In the Rheumatology Department at the Royal Hallamshire Hospital, Sheffield, UK mycophenolate mofetil (MMF), a reversible inhibitor of inosine monophosphate dehydrogenase necessary for the growth of B and T cells, has been used as an alternative immuno-suppressant. There is limited data supporting its effectiveness in patients with large vessel vasculitis (2), but anecdotal evidence from clinical practice in Sheffield has shown it to be effective. The aim of this retrospective study is to evaluate the effectiveness of MMF in the treatment of patients with large vessel vasculitis in terms of reduction in steroid dose, reduction in inflammation (C-reactive protein) and overall tolerability of the drug.MethodsA retrospective review of 35 patients with large vessel vasculitis (23 large vessel vasculitis, 5 temporal arteritis, 4 Takayasu's arteritis, 2 aortitis and 1 giant cell arteritis) taking MMF between January 2008 and December 2013 was undertaken. The patient list was created by searching electronically saved clinic letters for the keywords large vessel vasculitis, aortitis, Takayasu's, giant cell arteritis, temporal arteritis and mycophenolate mofetil. Reductions in steroid dose and CRP and adverse effects to MMF were assessed.ResultsThe patients, 29 women and 6 men with a mean age of 64, had been taking MMF in doses of between 1.5g once daily to 1.5g twice daily for between 1 and 10 years. MMF had a steroid sparing effect in 34 patients (97%) and in 6 cases the steroids were discontinued. 28 patients (80%) experienced a reduction in their CRP over the study period, and 21 (60%) had a CRP of less than 5 at the end of December 2013. The mean CRP at initiation of MMF was 24.1 and at the end of the study period it was 7.6. 28 patients continued taking MMF, 25 (71%) at the highest doses prescribed. 13 patients (37%) experienced adverse events whilst taking MMF, but these led to the termination of treatment in only 3 cases (9%). 4 patients (11%) had additional medications added in to the mycophenolate.ConclusionsMMF is an effective and well tolerated treatment for large vessel vasculitis. This retrospective review showed it to have a steroid sparing effect in 97% of patients and to lead to a reduction in CRP in 80%. 37% of patients experienced adverse events but these led to the discontinuation of MMF in only 9%. The results are comparable with those from previous studies demonstrating the effectiveness of MMF in the treatment of large vessel vasculitis, but they augment the evidence by incorporating larger patient numbers over a longer follow-up period.ReferencesMukhtyar C, Guillevin L, Cid M, et al. EULAR recommendations for the manangement of large vessel vasculitis. Annals of the Rheumatic Diseases 2009:68: 318-323.Kotter I, Henes J, Wagner A, et al. Does glucocorti...

No abstract

Background/Aims  Approximately 30-40% of rheumatology patients fail to respond to first-line biologics. Secondary inefficacy is mediated by immune complex formation between biologic agents and anti-drug antibodies. Anti-drug antibody testing has been undertaken at Sheffield Teaching Hospitals since October 2015. However, there are currently no national guidelines or consensus on what levels of anti-drug antibodies are clinically significant or what changes to therapy are suggested as a consequence of these tests. We aimed to review the reasons for and outcomes of anti-drug antibody levels tested at STH in patients on Adalimumab or Infliximab. Methods  Retrospective review of records of all Rheumatology patients having antidrug antibody levels tested October 2015 - April 2019. Results  237 patients were included in this analysis. The mean age of patients was 48 years. 43% were male. The most common reasons for testing antibody levels were clinical evidence of a flare in disease (n = 92) and patient reported worsening of symptoms (n = 88). 66% (n = 157) of antibody levels tested were negative, 21% (n = 49) of tests were strongly positive (antibody titre &gt;50). Serum drug concentrations were subtherapeutic in 20 % (n = 47), therapeutic in 22% (n = 51) and supratherapeutic in 38% (n = 91). In 51% of patients (n = 119) the current treatment regime was continued. However, 38% (n = 90) changed biologics, and dosing schedule was changed in 2% (n = 6). Antibody titres were more likely to be strongly positive in patients who had clinically active disease compared to those who had symptoms but no clinical evidence of disease (30% vs 10% p = 0.009). Those with strongly positive antibodies were more likely to switch biologics than those with normal antibodies (84% vs 28%, p = 0.01). Patients with clinically active disease but normal antibodies and drug levels were more likely to switch biologics than patients with no evidence of active disease but positive antibodies (p = 0.03). Underlying diagnosis (p = 0.23) or concomitant DMARD use (p = 0.92) were not associated with positive autoantibodies. Of the 47 patients with subtherapeutic drug levels, 61% (n = 29) had strongly positive anti-drug antibodies and 73% (n = 34) subsequently switched biologics. 49% (n = 111) of patients had both therapeutic drug levels and normal antibodies. Of these, 22% (n = 25) switched biologics. Of the 25 patients that switched biologics 24% (n = 6) did not have evidence of active disease and 76% (n = 19) had active disease. Conclusion  33% of patients had positive autoantibodies. 39% of patients switched biologics following testing. There was no protective effect of DMARDs identified. Patients with active disease were more likely to have positive antibodies and to switch biologics than those with no clinical evidence of disease. 25% of patients had subtherapeutic drug levels. However, only 2% of patients had a dose schedule adjustment. Therefore, dosing schedule alterations could be considered in these patients prior to escalating to a more expensive biologic. Disclosure  M. Cox: None. R. Smith: None. G. Wild: None. L. Dunkley: None.