ABSTRACT
Background/Aims Rheumatic and musculoskeletal diseases (RMDs) are some of the most common indications for prescribed opioids. It is unclear how opioid prescribing has changed in the UK for RMDs, especially during the COVID-19 pandemic with limited healthcare access and cancelled elective-surgical interventions, which could impact prescribing in either direction. We aimed to investigate trends in opioid prescribing in RMDs and assess the impact of the pandemic in the UK. Methods Adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), systemic lupus erythematosus (SLE), osteoarthritis (OA) and fibromyalgia with opioid prescriptions between 01/Jan/2006-31/Aug/2021 without prior cancer in the UK Clinical Practice Research Datalink (CPRD) were included. We calculated ageand gender-standardised yearly rates of people with opioid prescriptions between 2006-2021, and identified change points in trends by checking whether the rate of change of standardised rates crossed zero. For people with opioid prescriptions, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006-2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of people with opioid prescriptions between Jan/2015-Aug/2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic. Results We included 1,313,519 patients: 36,932 with RA, 12,649 with PsA, 6,811 with AxSpA, 6,423 with SLE, 1,255,999 with OA, and 66,944 with fibromyalgia. People with opioid prescriptions increased from 2006 to 2018 for OA, to 2019 for RA, AxSpA and SLE, to 2020 for PsA, and to 2021 for fibromyalgia, and all plateaued/decreased afterwards. OA patients on opioids increased from 466.8/10,000 persons in 2006 to a peak of 703.0 in 2018, followed by a decline to 575.3 in 2021. From 2006 to 2021, there was a 4.5-fold increase in fibromyalgia opioid users (17.7 vs.78.5/10,000 persons). In this period, MME/day increased for all RMDs, with the highest for fibromyalgia (>=35). During COVID-19 lockdowns, RA, PsA and fibromyalgia showed significant changes in the trend of people with opioid prescriptions. With a decreasing trend for RA (-0.001,95%CI=-0.002,-0.001) and a decreasing-to-flat curve for PsA (0.0010,95%CI=0.0006,0.0015) prepandemic until Feb/2020, the trends changed by -0.005 (95%CI=-0.008,-0.002) for RA and -0.003 (95%CI=-0.006,-0.0003) for PsA, leading to steeper decreasing trends during the pandemic (Mar/2020-Aug/2021). Fibromyalgia, conversely, had an increasing trend (0.009,95%CI=0.008,0.009) pre-pandemic, and this trend started decreasing by -0.009 (95%CI=-0.011,-0.006) during the pandemic. Conclusion The plateauing/decreasing trend of people with opioid prescriptions in RMDs after 2018 may reflect the efforts to tackle the rising opioid prescribing in UK primary care. Of all RMDs, fibromyalgia patients had the highest MME/day throughout the study period. COVID-19 lockdowns contribute to fewer people on opioids for most RMDs, reassuring there was no sudden increase in opioid prescribing during the pandemic.
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