Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study

Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Critically ill patients with and without SARS-CoV-2 better achieve energy and protein targets with a high-energy, high-protein peptide-based enteral tube feed;insights from a multicentre clinical audit performed during the COVID-19 pandemic

Meeting energy and protein requirements in critically ill patients is important for prognosis, yet difficult to achieve as a consequence of disease, management and/or altered nutritional intake[1]. Improvements in achieving energy and protein requirements with a high-energy, high-protein peptide-based tube feed were observed in community patients with impaired gastrointestinal function[2]. To establish whether this remained true in the critical care setting, where feeding intolerance is observed frequently in patients with[3] and without SARS-CoV-2[4], a retrospective multicentre audit was performed. Adults (> 18years) with or without SARS-CoV-2, admitted to critical care across 6 UK hospitals between May 2020 and December 2020, were retrospectively included if they received a peptide-based enteral tube feed (Nutrison Peptisorb Plus HEHP®, Nutricia Ltd), containing 1.5kcal/ml and 7.5g protein/100ml (herein referred to as HEHP). Data were collected from 15 critically ill patients (52±12y;87% male), with mean length of hospital stay being 26days (range: 7-49days). Of these, 10 were SARS-CoV-2 positive, with the remainder having pancreatitis (n=3), delayed gastric emptying (n=1) or unconfirmed diagnosis (n=1). HEHP was used second line (after whole protein) and indications (multiple were cited for some) for use included tolerance issues (n=10), elevated energy and protein requirements (n=5) or due to primary diagnosis (n=2). Estimated energy and protein intakes (% of requirements achieved) were recorded before and during use of HEHP. In addition, Dietitians were asked whether HEHP allowed patients to better meet their nutrient target Mean intake of HEHP was 2008±461kcal/day and 100±23g protein/day provided over a mean of 12days (range: 3-29days). The percentage of estimated energy and protein targets achieved increased albeit non significantly with the use of HEHP (from 76% before vs 87% during use of HEHP for both) and the direction of effect remained true regardless of SARS-CoV-2 status. Two thirds (67%, n=10 of 15) of Dietitians reported HEHP helped patients better meet their nutrient targets and 87% (n=13 of 15) of Dietitians perceived the high protein content of HEHP as beneficial for this patient group. Gastrointestinal tolerance (anecdotal reports) remained largely unchanged in approximately half of SARS-CoV-2 positive patients when using HEHP yet improved for others including non-SARS-CoV-2 patients. Enteral tube feeding in critically ill patients poses numerous difficulties, especially in SARS-CoV-2 positive patients. This audit in critically ill patients demonstrates that a high-energy, high-protein, peptide-based enteral tube feed can help complex patients better achieve energy and protein targets in patients with and without SARS-CoV-2. References 1.Pullen K, Colins R, Stone T et al. Are energy and protein requirements met in hospital? Clin Nutr 2017;31(2): 178-187. 2.Green B, Sorensen K, Phillips M et al. Complex Enterally Tube-Fed Community Patients Display Stable Tolerance, Improved Compliance and Better Achieve Energy and Protein Targets with a High-Energy, High-Protein Peptide-Based Enteral Tube Feed: Results from a Multi-Centre Pilot Study. Nutrients. 2020, 12, 3538. 3.Liu R, Paz M, Siraj L et al. Feeding intolerance in critically ill patients with COVID-19. Clin Nutr 2021. 4.Gungabissoon U, Hacquoil K, Bains C et al. Prevalence, Risk Factors, Clinical Consequences, and Treatment of Enteral Feed Intolerance During Critical Illness. J. Parenter. Enteral. Nutr. 2015, 39, 441–448.

A review of patients referred to Rheumatologywith haemophagocytic lymphohistiocytosis whowere treated with anakinra successfully

Background/AimsHaemophagocytic lymphohistiocytos (HLH) is a potentially life-threatening condition characterised by over-activation of the innate immunesystem. It can be classified into primary HLH, often inherited, orsecondary which is triggered by non-genetic causes, such as chronicimmunosuppression, malignancy or infection.Primary HLH is morefrequently observed in infants, however, secondary HLH is morecommonly observed in adults. Diagnosis is often delayed, most likelydue to the rarity of the condition and is usually prompted by serologicalabnormalities, including hyperferritinaemia, organ and bone marrowdysfunction.Treatment options are limited;however, the Royal FreeHospital has observed a number of secondary HLH cases who weresuccessfully treated with steroids and anakinra.MethodsA retrospective search of clinic letters and patient records wasundertaken using electronic care records. We also searched throughpharmacy records of patients treated with anakinra at the Royal FreeHospital. Patients with a documented diagnosis of HLH prior to March2020 who had been referred to Rheumatology were included. Weexcluded patients after March 2020 due to patients with COVID-19having similar overlap of symptoms and biomarkers as those withHLH. We identified key demographic details, laboratory, pathologyinvestigations, the course of hospital admission, primary diagnosis andfollow-up data. The diagnosis was confirmed withan H-score and bonemarrow biopsy where possible.ResultsWe identified nine adult cases with adocumented diagnosis of HLHwhohad been admitted to the Royal Free Hospitaland referred toRheumatology. They had allbeen subsequently followed up inoutpatientclinic.Ages of patients ranged from 19 to 58 with a male tofemale ratio of 2:1. The predominant underlying pathology wasadultonsetStill's disease(78%), with the remaining cases beingsecondary to HIV (22%). Bone marrow aspirate was performed in allpatients and 78% of patients aspirated had bone marrowappearancesin keeping with HLH.Ferritin levels varied from 532 micrograms/Lto93309 micrograms/L with a median ferritin of 5045.5 micrograms/L.HScores were variable witha median score of 171.5 (96-238).All patientsreceived steroids as part of their treatment. Anakinra (interleukin-1receptor antagonist) was delivered intravenously(6/9) or subcutaneously (3/9).ConclusionWe present data from nine cases of HLH treated with anakinra whosurvived their admission and have been subsequently followed up inclinic. We found that the majority of these patients had an underlyingdiagnosis of adult onset Still's disease. Anakinra was used successfully as part of their treatment both intravenously as well assubcutaneously. Further work is needed comparing patients withgood and poor outcomes to establish identifiable prognostic markersas well as effective treatment strategies.