Discontinuation of anti-tumour necrosis factor alpha treatment owing to blood test abnormalities, and cost-effectiveness of alternate blood monitoring strategies.

BACKGROUND: There is no evidence base to support the use of 6-monthly monitoring blood tests for the early detection of liver, blood and renal toxicity during established anti-tumour necrosis factor alpha (TNFα) treatment. OBJECTIVES: To evaluate the incidence and risk factors of anti-TNFα treatment cessation owing to liver, blood and renal side-effects, and to estimate the cost-effectiveness of alternate intervals between monitoring blood tests. METHODS: A secondary care-based retrospective cohort study was performed. Data from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) were used. Patients with at least moderate psoriasis prescribed their first anti-TNFα treatment were included. Treatment discontinuation due to a monitoring blood test abnormality was the primary outcome. Patients were followed-up from start of treatment to the outcome of interest, drug discontinuation, death, 31 July 2021 or up to 5 years, whichever came first. The incidence rate (IR) and 95% confidence intervals (CIs) of anti-TNFα discontinuation with monitoring blood test abnormality was calculated. Multivariate Cox regression was used to examine the association between risk factors and outcome. A mathematical model evaluated costs and quality-adjusted life years (QALYs) associated with increasing the length of time between monitoring blood tests during anti-TNFα treatment. RESULTS: The cohort included 8819 participants [3710 (42.1%) female, mean (SD) age 44.76 (13.20) years] that contributed 25 058 person-years (PY) of follow-up and experienced 125 treatment discontinuations owing to a monitoring blood test abnormality at an IR of 5.85 (95% CI 4.91-6.97)/1000 PY. Of these, 64 and 61 discontinuations occurred within the first year and after the first year of treatment start, at IRs of 8.62 (95% CI 6.74-11.01) and 3.44 (95% CI 2.67-4.42)/1000 PY, respectively. Increasing age (in years), diabetes and liver disease were associated with anti-TNFα discontinuation after a monitoring blood test abnormality [adjusted hazard ratios of 1.02 (95% CI 1.01-1.04), 1.68 (95% CI 1.00-2.81) and 2.27 (95% CI 1.26-4.07), respectively]. Assuming a threshold of £20 000 per QALY gained, no monitoring was most cost-effective, but all extended periods were cost-effective vs. 3- or 6-monthly monitoring. CONCLUSIONS: Anti-TNFα drugs were uncommonly discontinued owing to abnormal monitoring blood tests after the first year of treatment. Extending the duration between monitoring blood tests was cost-effective. Our results produce evidence for specialist society guidance to reduce patient monitoring burden and healthcare costs.

Is Vaccination Against COVID-19 Associated With Inflammatory Bowel Disease Flare? Self-Controlled Case Series Analysis Using the UK CPRD.

INTRODUCTION: To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and inflammatory bowel disease (IBD) flare. METHODS: Patients with IBD vaccinated against COVID-19 who consulted for disease flare between December 1, 2020, and December 31, 2021, were ascertained from the Clinical Practice Research Datalink. IBD flares were identified using consultation and corticosteroid prescription records. Vaccinations were identified using product codes and vaccination dates. The study period was partitioned into vaccine-exposed (vaccination date and 21 days immediately after), prevaccination (7 days immediately before vaccination), and the remaining vaccine-unexposed periods. Participants contributed data with multiple vaccinations and IBD flares. Season-adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) were calculated using self-controlled case series analysis. RESULTS: Data for 1911 cases with IBD were included; 52% of them were female, and their mean age was 49 years. Approximately 63% of participants had ulcerative colitis (UC). COVID-19 vaccination was not associated with increased IBD flares in the vaccine-exposed period when all vaccinations were considered (aIRR [95% CI] 0.89 [0.77-1.02], 0.79 [0.66-0.95], and 1.00 [0.79-1.27] in IBD overall, UC, and Crohn's disease, respectively). Analyses stratified to include only first, second, or third COVID-19 vaccinations found no significant association between vaccination and IBD flares in the vaccine-exposed period (aIRR [95% CI] 0.87 [0.71-1.06], 0.93 [0.75-1.15], and 0.86 [0.63-1.17], respectively). Similarly, stratification by COVID-19 before vaccination and by vaccination with vectored DNA or messenger RNA vaccine did not reveal an increased risk of flare in any of these subgroups. DISCUSSION: Vaccination against COVID-19 was not associated with IBD flares regardless of prior COVID-19 infection and whether messenger RNA or DNA vaccines were used.

Do ß-adrenoreceptor blocking drugs associate with reduced risk of symptomatic osteoarthritis and total joint replacement in the general population? A primary care-based, prospective cohort study using the Clinical Practice Research Datalink.

INTRODUCTION: To investigate if ß-adrenoreceptor blocking drug (ß-blocker) prescription reduces the risk of knee or hip osteoarthritis, total joint replacement and analgesic prescription. SETTING: Primary care. METHODS AND ANALYSIS: This is a cohort study using data from the Clinical Practice Research Datalink. Two separate analyses will be performed. Study 1 will be on the association between ß-blocker prescription and incident knee/hip osteoarthritis. Inclusion criteria will be age ≥40 years. Exposed participants will be those with ≥2 continuous ß-blocker prescriptions, and the index date will be the date of the first prescription of ß-blocker. Unexposed participants will include up to four controls matched for age, sex, general practice surgery and propensity score for ß-blocker prescription. Exclusion criteria will include contraindications to ß-blockers, consultations for osteoarthritis or potent analgesic prescription before the index date. Outcomes will be knee osteoarthritis (primary outcome), hip osteoarthritis, knee pain and hip pain. Study 2 will be on the association between ß-blocker prescription and total joint replacement and analgesic prescription in people with osteoarthritis. Inclusion criteria will be age ≥40 years, knee or hip osteoarthritis, and index date will be as in study 1. Unexposed participants will be as in study 1, additionally matched for consultation for knee or hip osteoarthritis prior to the index date. Exclusion criteria will include contraindications to ß-blockers and osteoarthritis in other joints prior to the index date. Outcomes will be total knee replacement (primary outcome), total hip replacement and new analgesic prescription. STATISTICAL ANALYSIS: Kaplan-Meier curves will be plotted, and Cox proportional HRs and 95% CIs will be calculated. Stratified analysis will be performed by class of ß-blocker, intrinsic sympathomimetic effect and indication(s) for prescription. ETHICS AND DISSEMINATION: This study was ethically approved by the Independent Scientific Advisory Committee of the Medicines and Healthcare Authority (Ref 18_227R). The results of this study will be published in peer-reviewed journals and presented at conferences. SUMMARY: This prospective cohort study will evaluate the analgesic potential of commonly used drugs for osteoarthritis pain.

Implication of nurse intervention on engagement with urate-lowering drugs: A qualitative study of participants in a RCT of nurse led care.

OBJECTIVES: To explore patient perception of the role of a nurse-led complex package of care in facilitating engagement with urate-lowering therapies (ULTs) in the management of gout. METHODS: Thirty people who had participated in a randomised controlled trial investigating the effect of a nurse-led complex package of care for gout, were purposively sampled and interviewed between 18-26 months after the end of the trial. Interviews were recorded, transcribed and analysed using a modified grounded-theory approach. Data were managed using Nvivo. STATA v15 was used to describe summary statistics. RESULTS: Participants described their views and experiences of engaging with a nurse-led intervention designed to provide holistic assessment, individualised patient education, and involvement in shared decision-making for the long-term management of gout. The analysis revealed key themes in how nurse-led intervention facilitated engagement with ULT, namely by proving improved knowledge and understanding of gout and its treatment, involvement of patients in decision-making about treatment, and increased confidence about benefits from treatment. However, some treatment uncertainty and concern remained and one participant free of gout flares discontinued ULT, while another halved the dose after the end of the trial. CONCLUSIONS: This study reports data on patient experience of engaging with ULT to manage gout after receiving nurse-led care. It demonstrates that shared decision-making and the joint efforts of fully informed practitioners and patients persuades patients to engage with ULTs, and that experiencing the benefits of curative treatment motivates them to maintain adherence.

Association between benzodiazepine use and exacerbations and mortality in patients with asthma: a matched case-control and survival analysis using the United Kingdom Clinical Practice Research Datalink.

PURPOSE: To investigate the association between the gamma-aminobutyric acid (GABA)ergic drugs, benzodiazepines or zopiclone and the occurrence of asthma exacerbations and subsequent mortality in a cohort of asthma patients. METHODS: The number of patients that were included were 105,747 for those without asthma exacerbation and 25,895 for those with exacerbated asthma. A nested case-control study probed the association between benzodiazepines or zopiclone and occurrence of asthma exacerbation (primary outcome) using conditional logistic regression. Cox regression was used to determine the association between the drugs and all-cause mortality in patients with recorded asthma exacerbation. Adjusted matched odds ratios (adj mOR) and adjusted hazard ratios (adj HR) with 95% confidence intervals (CI) are presented. RESULTS: Current benzodiazepine use was associated with increased occurrence of asthma exacerbation (adj mOR 1.49; 95%CI [1.15, 1.93]; P = 0.001) as was current zopiclone use (adj mOR 1.59; 95%CI [1.37, 1.85]; P < 0.001). In patients with an asthma exacerbation, current benzodiazepine use was associated with increased all-cause mortality during a median follow-up of 2 years (adj HR 2.78; 95%CI [1.26, 6.12]; P = 0.011), and the association between zopiclone use and all-cause mortality showed borderline statistical significance (adj HR 1.58; 95%CI [0.98, 2.54]; P = 0.058). CONCLUSION: Benzodiazepines and zopiclone may increase the likelihood of asthma exacerbation, and benzodiazepines may also increase the likelihood of mortality following exacerbation. These data suggest that caution should be exercised when prescribing benzodiazepines to patients with asthma.