Even low doses of steroids increase the risk of cardiovascular disease in people with inflammatory diseases

The study Pujades-Rodríguez M, Morgan AW, Cubbon RM, Wu J. Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: a population-based cohort study. PLoS Med 2020;17:e1003432. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/low-doses-steroids-increase-cardiovascular-risks-in-inflammatory-diseases/

Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients on non-vitamin K oral anticoagulants

ObjectiveGastrointestinal bleeding (GIB) risk in relation to concomitant treatment with non-vitamin K oral anticoagulants (NOAC) and oral glucocorticoids is insufficiently explored. We aimed to investigate the short-term risk following coexposure.MethodsThis is a register-based, nationwide Danish study including patients with atrial fibrillation on NOACs during 2012–2018. Patients were defined as exposed to oral glucocorticoids if they claimed a prescription within 60 days prior to GIB. We investigated the associations between GIB and oral glucocorticoid exposure, reporting HRs via a nested case–control design and absolute risk via a cohort design. Matching terms were age, sex, calendar year, follow-up time and NOAC agent.Results98 376 patients on NOACs (median age: 75 years (IQR: 68–82), 44% female) were included, and 16% redeemed at least one oral glucocorticoid prescription within 3 years. HRs of GIB were increased comparing exposed with non-exposed patients (<20 mg daily dose, HR 1.54 (95% CI 1.29 to 1.84); ≥20 mg daily dose, HR 2.19 (95% CI 1.81 to 2.65)). 60-day standardised absolute risk of GIB following first claimed oral glucocorticoid prescription increased compared with non-exposed: 60-day absolute risk: 0.71% (95% CI 0.58% to 0.85%) vs 0.38% (95% CI 0.32% to 0.43%). The relative risk was elevated as well: risk ratio of 1.89 (95% CI 1.43 to 2.36).ConclusionsConcomitant treatment with NOACs and oral glucocorticoids was associated with a short-term rate and risk increase of GIB compared with patients only on NOACs. This could have implications for clinical management, necessitating closer monitoring or other risk mitigation strategies during episodes of cotreatment with oral glucocorticoids.

Glucocorticoid toxicity reduction with Mepolizumab using the glucocorticoid toxicity index

Reduction in glucocorticoid exposure is the primary benefit of new biologic treatments in severe asthma, but there is currently no evidence that reduction in glucocorticoid exposure corresponds to a proportionate reduction in associated toxicity.ObjectivesTo use the validated Glucocorticoid Toxicity Index (GTI) to assess change in glucocorticoid toxicity after 12 months treatment with mepolizumab, and compare toxicity change to glucocorticoid reduction and change in patient reported outcome measures (PROMs).MethodsA longitudinal, real world prospective cohort of 101 consecutive patients with severe asthma commenced on mepolizumab in a Specialist UK Regional Severe Asthma clinic. GTI toxicity assessment, cumulative glucocorticoid exposure and PROMs were recorded on commencing mepolizumab (V1), and after 12 months treatment (V2).ResultsThere was significant reduction in oral glucocorticoid exposure (V1 4280 mg prednisolone/year [interquartile range (IQR) 3083, 5475] versus V2 2450 mg prednisolone/year [1243, 3360], p<0.001). Substantial improvements in individual toxicities were observed but did not correlate with oral glucocorticoid reduction. Mean GTI Aggregate Improvement Score (AIS) was −35.7 (sd 57.8) with a wide range in toxicity change at individual patient level (AIS range −165 to +130); 70% (71/101) had a reduction in toxicity (AIS <0), 3% (3/101) had no change (AIS=0) and 27% (27/101) an increase in overall toxicity. Sixty-two (62/101) patients met the AIS minimally clinically important difference of ≤−10, but AIS did not correlate with glucocorticoid reduction or change in PROMs.ConclusionMepolizumab resulted in substantial oral glucocorticoid reduction but this did not correlate with reduction in oral glucocorticoid toxicity, which varies widely at the individual patient level. Oral glucocorticoid reduction is not a comprehensive measure of response to mepolizumab.

Reappraisal of the Prognostic Factors of Outcome and Recovery Time in Patients with Idiopathic Bell’s Palsy: A Retrospective Single-Center Analysis

Study Objectives: This retrospective study investigated prognostic factors and recovery time in patients with Bell’s palsy after different doses and durations of oral glucocorticoid treatments. Subjects and Methods: A total of 396 patients initially diagnosed with Bell’s palsy that had visited the Department of Neurology of Chang Gung Memorial Hospital, Taoyuan, a tertiary referral medical center in Taiwan, between January 2014 and December 2018 were included. Medical records, facial electroneurography (fENoG), and blink reflex (BR) tests were reviewed and analyzed. A favorable outcome was defined as patients who improved to grade ≤ II, and an unfavorable outcome was defined as patients who improved to grade ≥ III in 6 months according to the House–Brackmann (HB) grading system. Results: The rate of favorable outcomes was 89.4% (354 of 396 patients) at the 6-month follow-up. A favorable outcome (HB less than grade II) was associated with a delayed BR (odds ratio, OR, 5.38; 95% CI, 1.82 to 15.90) and fENoG values (the lesion side/the healthy side) over 33% (OR, 6.67; 95% CI, 3.02 to 14.71). The recovery time was significantly shorter for those with a delayed BR than for those with an absent BR and shorter for those with good fENoG values (>33%) than for those with poor values (≤33%). However, treatment without or with different doses and durations of oral glucocorticoid did not influence the final outcome or recovery time in this study. Conclusions: The fENoG and BR tests were significant and highly valuable examinations for predicting the final outcome. Moreover, age younger than 60 years, a delayed BR, and fENoG values > 33% were associated with shorter recovery times.

MON-159 High Mortality Rate in Oral Glucocorticoid Users: A Case-Control Study

Objective. Long-term oral glucocorticoid (GC) use is associated with increased mortality in patients with rheumatoid arthritis and inflammatory bowel disease. The aim of the study was to investigate whether there is excess mortality among oral GC users, regardless of the underlying disease. Methods. This was a retrospective case-control study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. Patients receiving ≥5 mg prednisolone (or equivalent dose of other GC) daily for ≥21 days between 2007-2014 were included. For each patient, a control person, matched for age and sex, was included. The cause of death was obtained from the Swedish Cause-of-Death Registry. Hazard ratio (HR) for mortality was calculated by using Cox proportional hazard model and by the log-rank test. The GC users were divided into four groups according to the length of GC treatment: 1) single-occasion users 2) occasional users (&lt;300 tablets/year); 3) medium-term users (&gt; 300 tablets/year for ≤ 2 consecutive years); and 4) long-term users (&gt;300 tablets/year for &gt; 2 consecutive years). Results. Of 1,585,335 inhabitants in Western Sweden, 223,211 GC users (women 55.6%) were identified for the analysis. The mean age was 48 ± 24 years. Median follow-up time was 3.6 years for GC users and 3.9 years for matched controls. The overall HR for death in oral GC users was 2.26 (95% CI 2.21-2.31). After exclusion of patients with malignant neoplasm, the HR for death was 1.41 (95% CI 1.38-1.45); 1.33 (95% CI 1.27-1.38) in single-occasion GC users (n=112,196), 1.36 (95% CI 1.30-1.42) in occasional users (n=63,862), 1.89 (95% CI 1.79-1.99) in medium-term users (n=19,129) and 1.67 (95% CI 1.51-1.84) in long-term users (n=7,191). The highest HRs were observed for deaths from heart failure (HR 1.71, 95% CI 1.63-1.80), sepsis (HR 1.71, 95% CI 1.51-1.94), and pulmonary embolism (HR 1.87, 95% CI 1.58-2.21). Conclusion. GC users have excess mortality compared to the background population. This illustrates the importance of surveillance for patients on oral GC treatment where adverse effects should be monitored and, when indicated, appropriately treated.