Corticosteroid-associated Adverse Events Research Articles

Low- Versus High-Dose Methylprednisolone in Adult Patients With Coronavirus Disease 2019: Less Is More

BackgroundCorticosteroids use in severe coronavirus disease 2019 (COVID-19) improves survival; however, the optimal dose is not established. We aim to evaluate clinical outcomes in patients with severe COVID-19 receiving high-dose corticosteroids (HDC) versus low-dose corticosteroids (LDC).MethodsThis was a quasi-experimental study conducted at a large, quaternary care center in Michigan. A corticosteroid dose change was implemented in the standardized institutional treatment protocol on November 17, 2020. All patients admitted with severe COVID-19 that received corticosteroids were included. Consecutive patients in the HDC group (September 1 to November 15, 2020) were compared to the LDC group (November 30, 2020 to January 20, 2021). High-dose corticosteroids was defined as 80 mg of methylprednisolone daily in 2 divided doses, and LDC was defined as 32–40 mg of methylprednisolone daily in 2 divided doses. The primary outcome was all-cause 28-day mortality. Secondary outcomes included progression to mechanical ventilation, hospital length of stay (LOS), discharge on supplemental oxygen, and corticosteroid-associated adverse events.ResultsFour-hundred seventy patients were included: 218 (46%) and 252 (54%) in the HDC and LDC groups, respectively. No difference was observed in 28-day mortality (14.5% vs 13.5%, P = .712). This finding remained intact when controlling for additional variables (odds ratio, 0.947; confidence interval, 0.515–1.742; P = .861). Median hospital LOS was 6 and 5 days in the HDC and LDC groups, respectively (P < .001). No differences were noted in any of the other secondary outcomes.ConclusionsLow-dose methylprednisolone had comparable outcomes including mortality to high-dose methylprednisolone for the treatment of severe COVID-19.

PCV5 Risk Factors Associated with Recurrence and Corticosteroid-Associated Adverse Events in Patients with Recurrent Pericarditis

Recurrent pericarditis (RP) occurs in up to 30% of acute pericarditis patients with some experiencing multiple recurrences and/or complications. Treating RP with corticosteroids can increase adverse events, risk of recurrence, and potentially healthcare resource utilization. This retrospective study examined risk factors for recurrence and corticosteroid-related adverse events (CS-AEs) among RP patients.

Integrating high dose inhaled corticosteroids into oral corticosteroids stewardship

Uncertainties still surround high dose inhaled corticosteroids (ICS) use in asthma. In hindsight, certain aspects of the ICS development story can help elucidate why. In 1973, Cameron et al. [1] signed a brilliant paper reporting the results of a double blind, randomised controlled trial demonstrating the oral corticosteroid (OCS)-sparing effect of ICS as the primary outcome. A few years later, the assessment of this benefit was mitigated when a complete weaning of OCS remained unachievable [2]. The benefit of ICS was therefore understood to be mostly based on an improved safety profile purportedly due to reduced systemic diffusion. Thus, the understanding of how ICS was of any benefit to asthma patients when compared to OCS was mostly based on a greater safety profile supposedly due to a reduced systemic diffusion. Similarly, topically administered corticosteroids were also developed in the same time period for diseases affecting the skin, the eyes, the nose or the joints. As for ICS, whether or not these formulations reduce corticosteroid-associated adverse events remains largely debated [3]. If high doses of ICS are equivalent to low dose OCS, they should be considered as such <http://bit.ly/2CYssfB>

Safety Considerations with the Use of Corticosteroids and Biologic Therapies in Mild-to-Moderate Ulcerative Colitis.

The risk of corticosteroid-associated adverse events can limit the use of systemic corticosteroids. Oral, topically acting, second-generation corticosteroids that deliver drug to the site of inflammation, and biologic therapies, are effective treatment alternatives. The aim of this review was to evaluate the safety and tolerability of topically acting corticosteroids and biologic therapies versus oral systemic corticosteroids for ulcerative colitis (UC). The PubMed database was searched for clinical and observational trials, systematic reviews, and case reports/series published between January 1950 and September 30, 2016. Search terms used included "corticosteroids," "beclomethasone dipropionate," "budesonide," "infliximab," "adalimumab," "golimumab," and "vedolizumab" in combination with "ulcerative colitis" or "inflammatory bowel disease." A total of 582 studies were identified from PubMed searches. Only 1 direct comparative trial for oral topically acting corticosteroids and systemic corticosteroids was available, and no comparative trials versus biologic therapies were identified. In patients with mild-to-moderate UC, short-term (4-8 wk) oral beclomethasone dipropionate or oral budesonide multimatrix system demonstrated safety profiles comparable with placebo with few corticosteroid-related adverse events reported. Based on long-term data in patients with moderate-to-severe UC, biologics have a generally tolerable adverse event profile, although infections, infusion reactions, and autoimmune disorders were frequently reported. Second-generation corticosteroids, beclomethasone dipropionate and budesonide multimatrix system, exhibited a favorable safety profile in patients with mild-to-moderate UC. For biologics, which are only indicated in moderate-to-severe UC, additional studies are needed to further ascertain the benefit to risk profile of these agents in patients with mild-to-moderate disease (see Video Abstract, Supplemental Digital Content, http://links.lww.com/IBD/B653).

Abiraterone acetate and prednisone in chemotherapy-naïve prostate cancer patients: rationale, evidence and clinical utility.

Abiraterone acetate 1000 mg/day, combined with prednisone 5 mg PO twice daily, is indicated for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate is the oral prodrug of abiraterone, a specific CYP17 inhibitor that blocks androgen biosynthesis within the adrenal glands, testes and tumor microenvironment. In a phase III trial of men with asymptomatic or minimally symptomatic, chemotherapy-naïve mCRPC, treatment with oral abiraterone acetate plus prednisone led to a statistically significant improvement in the co-primary endpoints of overall survival and radiographic progression-free survival when compared with placebo plus prednisone. In long-term follow-up of phase III trials, the incidence of corticosteroid-associated adverse events was 25.5% in the abiraterone acetate plus prednisone arm compared with 23.3% in the placebo plus prednisone arm. The need for regular patient monitoring and appropriate management of symptoms during long-term use of prednisone must be placed in context with the improvement in survival seen with abiraterone plus prednisone. Within the multidisciplinary environment that is emerging to meet quality and cost imperatives, abiraterone acetate plus prednisone is suitable for use in the chemotherapy-naïve population with minimal symptoms as well as in patients who have been treated with docetaxel and may have symptomatic disease. Ongoing trials are evaluating the role of abiraterone acetate plus prednisone in patients with nonmetastatic CRPC and metastatic hormone-sensitive prostate cancer, while further trials in the mCRPC setting are evaluating its use in combination regimens.

Steroids in fluid and/or vasoactive infusion dependent pediatric shock: study protocol for a randomized controlled trial.

BackgroundPhysicians often administer corticosteroids for the treatment of fluid and vasoactive infusion dependent pediatric shock. This use of corticosteroids is controversial, however, and has never been studied in a pediatric randomized controlled trial (RCT). This pilot trial will determine the feasibility of a larger RCT on the role of corticosteroids in pediatric shock.Methods/designSteroids in Fluid and/or Vasoactive Infusion Dependent Pediatric Shock (STRIPES) is a pragmatic, seven-center, double-blind, pilot RCT. We aim to randomize 72 pediatric patients with fluid and vasoactive infusion dependent shock to receive either hydrocortisone or a saline placebo for 7 days or until clinical stability, whichever occurs first. The primary outcome of this pilot trial is the feasibility of recruitment, defined as the number of patients enrolled over a 1-year period. Secondary outcomes include the frequency of, and reasons for, open-label steroid use, protocol adherence, incidence of mortality and corticosteroid-associated adverse events, time to discontinuation of inotropes, and feasibility of blood sampling.DiscussionCorticosteroids are used for the treatment of pediatric shock without sufficient evidence to support this practice. While there is a scientific rationale and limited data supporting their use in this setting, there is also evidence from other populations suggesting potential harm. The STRIPES pilot study will assess the feasibility of a larger, much needed trial powered for clinically important outcomes.Trial registrationClinicalTrials.gov: NCT02044159Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1365-6) contains supplementary material, which is available to authorized users.

Low Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration-resistant Prostate Cancer

BackgroundAbiraterone acetate (AA) is the prodrug of abiraterone, which inhibits CYP17A1 and testosterone synthesis and prolongs the survival of patients with metastatic castration-resistant prostate cancer (mCRPC). AA plus prednisone (P) (AA+P) is approved for the treatment of patients with mCRPC. ObjectiveTo investigate whether long-term use of low-dose P with or without AA leads to corticosteroid-associated adverse events (CA-AEs) in mCRPC patients. Design, setting, and participantsThe study included 2267 patients in COU-AA-301 and COU-AA-302. We used an inclusive Standardized MedDRA Queries–oriented approach to identify 112 preferred terms for known CA-AEs, and assessed the incidence of CA-AEs during 3-mo exposure intervals and across all P exposure levels. InterventionAll 2267 patients received 5mg of P twice daily, and 1333/2267 received AA (1g) plus P. Results and limitationsThe CA-AE incidence after any P exposure was 25%, 26%, and 23% for any grade, and 5%, 5%, and 4% for grade ≥3 CA-AEs for all patients and the AA+P and P alone groups, respectively. The most common any-grade CA-AEs were hyperglycemia (7.4%, 7.8%, and 6.9% for all patients, AA+P, and P alone, respectively) and weight increase (4.3%, 3.9%, and 4.8%, respectively). When assessed by duration of exposure (3-mo intervals up to ≥30 mo), no discernable trend was observed for CA-AEs, including hyperglycemia and weight increase. The investigator-reported study discontinuation rate due to CA-AEs was 11/2267 (0.5%), and one patient had a CA-AE resulting in death. ConclusionsLow-dose P given with or without AA is associated with low overall incidence of CA-AEs. The frequency of CA-AEs remained low with increased duration of exposure to P. Patient summaryWe assessed adverse events in patients with metastatic castration-resistant prostate cancer during long-term treatment with a low dose of a corticosteroid. We found that long-term treatment with this low-dose corticosteroid is safe and tolerable.

Anti-tumor necrosis factor agents reduce corticosteroid use compared with azathioprine in patients with Crohn’s disease

Background:Corticosteroids are effective for inducing remission of Crohn’s disease, but should not be used long term due to risk of adverse events. Benefits of immunosuppressants (e.g., azathioprine) and anti tumor necrosis factor (anti-TNF) agents include reduced reliance on corticosteroid-based therapies and avoidance of corticosteroid-associated adverse events. Our aim was to evaluate corticosteroid-sparing effects in patients with Crohn’s disease upon being newly initiated on an anti-TNFα agent or azathioprine.Methods:An analysis of US patient claims data from January 2008 to October 2011 was conducted using Truven Health MarketScan Research databases. Corticosteroid-sparing within 12 and 24 months after initiation of an anti-TNF agent (adalimumab, certolizumab pegol, or infliximab) or azathioprine was evaluated.Results:In total, 2900 patients received a prescription for corticosteroids within the 6 month period before the initiation of an anti-TNF agent (63%) or azathioprine (37%). When certolizumab pegol, infliximab, or adalimumab were collectively compared with azathioprine, patients initiated on an anti-TNF agent avoided further prescriptions for corticosteroids at a greater rate than patients receiving azathioprine at 12 (43% vs. 27%, respectively; P < 0.0001) and 24 months (33% vs. 23%, respectively; P = 0.028). Individually, all anti-TNF agents showed higher rates of corticosteroid-sparing compared with azathioprine at 12 (P < 0.0001–0.011), but not 24 months (P = 0.0086–0.24). Key limitations of this study include lack of data regarding disease severity, response and assumptions of improvement, and compliance.Conclusions:Patients with Crohn’s disease were able to avoid new prescriptions for corticosteroids at a statistically higher rate when treated with an anti-TNF agent. These results demonstrate that the anti-TNF agents are superior to azathioprine for minimizing exposure to corticosteroids.

Burden of corticosteroid use in patients with systemic lupus erythematosus: results from a Delphi panel.

Corticosteroid-related adverse events (AEs) are commonly reported in systemic lupus erythematosus (SLE), but are often under-represented in claims data. The most common corticosteroid-related AEs are not necessarily the most costly. The present study aimed to examine corticosteroid-related AE rates and identify the associated cost consequences in patients with SLE from the perspective of rheumatologists treating SLE in the United States (US). A modified Delphi process and RAND Appropriateness Method was used to estimate corticosteroid-related AEs and costs based on data from SLE-treating US rheumatologists and estimates from alternative sources. The panel (n=10) participated in two web-based questionnaires, covering disease severity, corticosteroid use, corticosteroid-related AEs, and resource utilization associated with treatment of the AEs. Eight members of the panel then participated in a guided discussion by interactive teleconference, in which the costs associated with specific corticosteroid-related AEs were also discussed. Consensus was achieved in the teleconference when a single response category (consensus values from 1 to 4 [4=strongly agree, 1=strongly disagree]) accounted for ≥80% of responses. Thirteen consensus statements were developed following two Delphi rounds. Costs were estimated for eight corticosteroid-associated AEs from the panel of rheumatologists. In the patients with SLE treated by these physicians, 41.5% were considered to have mild disease, 36.5% moderate disease, and 22.0% severe disease. The number of specialist visits, corticosteroid use, and corticosteroid dose increased with disease severity. The estimated rates of all AEs (except for cataracts) were at least doubled in patients receiving corticosteroid doses>20 mg/day compared with ≤20 mg/day. The highest estimated mean total costs of an event (for the required treatment duration for one patient) were for avascular necrosis ($14,460) and serious infection ($11,660). The costs of more common AEs, such as osteoporosis, obesity, diabetes, and fractures, ranged from $1190 to $8220. Ten rheumatologists concluded that as disease severity increases, corticosteroid doses increased. Greater utilization of resources is needed to manage patients and corticosteroid-related AEs.

PND12 the Cost of Corticosteroid-associated Adverse Events in Systemic Lupus Erythematosus

PND12 the Cost of Corticosteroid-associated Adverse Events in Systemic Lupus Erythematosus

Incidence and US Costs of Corticosteroid-Associated Adverse Events: A Systematic Literature Review

Objective The objective of this systematic literature review was to evaluate the incidences and risks for adverse events (AEs) associated with oral and parenteral corticosteroids. An assessment was performed to estimate the costs of such AEs. Methods A systematic review of literature published from 2007 to 2009 was conducted to identify the incidence rates and risk ratios of corticosteroid-related AEs. The review protocol was developed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The literature search was expanded to include additional search terms for psychiatric conditions, infections, and peptic ulcers. Costs obtained from a separate narrative literature review were applied to AEs likely to affect third-party payers in the United States. Results A total of 357 publications were identified from the primary (n = 323) and secondary (n = 34) searches. Of these, 310 were excluded because they did not evaluate AEs related to corticosteroids, were an excluded publication type, or for other reasons. A final list of 47 studies were used for data extraction. Across patient populations, the most frequently reported corticosteroid-associated AEs were psychiatric events, infections, gastric conditions, and fractures. Corticosteroid-associated AEs reported to occur at an incidence >30% were sleep disturbances, lipodystrophy, adrenal suppression, metabolic syndrome, weight gain, and hypertension. Vertebral fractures were reported at an incidence of 21% to 30%. Dose-response relationships were documented for fractures, acute myocardial infarction, hypertension, and peptic ulcer. The costs of managing AEs that may occur with corticosteroids can be substantial. The literature reported 1-year per-patient costs of up to $26,471.80 for nonfatal myocardial infarction, and per-event costs as high as $18,357.90 for fracture. The findings from the present review should be interpreted cautiously due to several limitations, including the retrospective design of most of the studies identified, risk for confounding due to underlying disease activity or patient population, and the relatively small number of studies that reported each AE association. As this cost analysis was preliminary, a comprehensive pharmacoeconomic analysis should be undertaken to confirm the findings. Conclusion Based on the findings from this review, systemic corticosteroids are a common cause of AEs that may be costly to payers.

The effectiveness of budesonide therapy for Crohn's disease.

To assess the effectiveness and safety of budesonide in comparison to corticosteroids, 5-aminosalicylic acid (5-ASA), or placebo for inducing remission of active Crohn's disease and for maintaining remission. Randomized controlled trials comparing budesonide to corticosteroids, 5-ASA products or placebo were included. Trials had to report on the effectiveness of treatment (defined as decreasing or maintaining Crohn's Disease Activity Index, CDAI, scores < or = 150) or adverse events. After assessing the validity of study design and independent, duplicate data extraction from selected trials, summary relative risks (RR) were calculated for each outcome. A test of heterogeneity was also calculated for each outcome using a random effects model. Budesonide was more likely to induce remission than placebo (RR=1.82, 95% CI: 1.15-2.88) or 5-ASA (RR=1.73, 95% CI: 1.26-2.39), although only one trial compared budesonide to 5-ASA products. Although budesonide induced remission less frequently than conventional corticosteroids (RR=0.87, 95% CI: 0.76-0.995), there was no significant difference between conventional corticosteroids and budesonide for inducing remission among patients with a low disease activity (initial CDAI=200-300). Budesonide was significantly less likely to cause corticosteroid-associated adverse events than conventional corticosteroids (RR=0.65, 95% CI: 0.53-0.80). No significant difference in total adverse events or corticosteroid-associated adverse events was demonstrated between budesonide and 5-ASA or placebo. Budesonide is significantly more effective than placebo or 5-ASA for inducing remission of active Crohn's disease. Although budesonide is 13% less effective for the induction of remission in active Crohn's disease than conventional corticosteroids, it is less likely to cause corticosteroid-related adverse effects. Budesonide is ineffective in maintaining remission.

Preoperative and postoperative medications used for cataract surgery.

The current state of cataract surgery for the millennium may be stated as "minimally invasive techniques." This review presents recent articles on the perioperative use of antibiotics (primarily fluoroquinolones), nonsteroidal antiinflammatory drugs (Voltaren and ketorolac), and new corticosteroids (rimexolone and loteprednol etabonate). Preoperative topical application of ofloxacin or ciprofloxacin results in a satisfactory minimal inhibitory concentration for most pathogens. However, one cannot determine the actual effect of intraoperative antibiotics on acute postoperative endophthalmitis, because of its low overall incidence. Nonsteroidal antiinflammatory drugs, especially Voltaren, may offer equivalent antiinflammatory efficacy (for both postoperative inflammation and cystoid macular edema) without the typically corticosteroid-associated adverse events. Rimexolone and loteprednol etabonate, two new corticosteroids, may offer good antiinflammatory efficacy with greatly reduced risk for elevation of intraocular pressure.