ABSTRACT
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
ABSTRACT
Background/Aims Secukinumab has demonstrated long-lasting efficacy and a favorable safety profile in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). SERENA is an ongoing, longitudinal, observational study in>2900 patients with moderate to severe psoriasis, active PsA, and AS. We report interim data on impact of intermediate treatment interruption on secukinumab effectiveness in patients with active PsA or AS. Methods This analysis included data for 534 PsA and 470 AS patients enrolled in SERENA between Oct 2016 and Oct 2018 and followed-up for at least 2 years. Patients (≥18 years) with active PsA or AS were required to have received ≥16 weeks of secukinumab treatment before enrolment. Treatment interruption was defined as interruption of secukinumab therapy for at least 3 months between the last injection and re-initiation. Effectiveness assessments included swollen and tender joint count in PsA patients, and Patient Global Assessment (PtGA) and BASDAI score in AS patients before and during treatment interruption and post secukinumab re-initiation. Patients with assessments in≥2 of the time periods were included. Last assessment prior to intermediate treatment interruption was used as baseline. The assessment closest to 6 months after re-initiation was considered the post-secukinumab re-initiation assessment. Results A total of 31 (5.8%) PsA patients and 42 (8.9%) AS patients had an intermediate treatment interruption since initiation of secukinumab treatment. The mean (SD) duration of treatment interruption was 24.8 (16.4) and 26.4 (22.9) weeks for PsA and AS patients, respectively. The mean (SD) duration of secukinumab treatment before the treatment interruption was 86.8 (50.3) and 90.2 (46.9) weeks, and after the treatment interruption was 73.6 (44.4) and 63.2 (46.8) weeks. The most commonly reported reasons included adverse events (AEs;18 [58.1%] PsA, 19 [45.2%] AS), patient decision (3 [9.7%] PsA, 3 [7.1%] AS), and COVID-19 outbreak-related reasons (1 [3.2%] PsA, 6 [14.3%] AS patients). More than 80% of PsA patients and 76% of AS patients reinitiated secukinumab without a loading phase after the treatment interruption. The swollen and tender joint count increased in PsA patients from the last assessment prior to the treatment interruption (1.3 [1.0] and 7.2 [11.4];n=6) to the first assessment during the treatment interruption (4.0 [1.4] and 16.5 [19.1];n=2), and gradually decreased post secukinumab re-initiation (0.4 [0.5] and 2.0 [0.7];n=5). PtGA and BASDAI remained stable in AS patients from the last assessment prior to the treatment interruption to the first assessment during the treatment interruption and after secukinumab re-initiation. Conclusion Secukinumab intermediate treatment interruption occurred due to a variety of reasons in the real-world setting, mainly AEs and patient decision. Most patients re-initiated secukinumab treatment without a loading phase. No notable impact of the intermediate treatment interruption was observed on the effectiveness of secukinumab.