Corticosteroid Dose In Patients Research Articles

Replacing Steroids in Transplant-Ineligible Multiple Myeloma: The Phase 2 Isatuximab-Bortezomib-Lenalidomide-Dexamethasone Rest Study

Background: Standard therapies for patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplantation (ASCT) have been lenalidomide-dexamethasone (Rd), bortezomib-lenalidomide-dexamethasone (VRd) or bortezomib-melphalan-prednisone (VMP). The benefit of adding an anti-CD38 monoclonal antibody (mAb) to the standard treatments of VMP and Rd has been demonstrated in two large phase 3 studies, achieving overall response rates (ORR) of 90.9% and 92.9% in the daratumumab-VMP arm and the daratumumab-Rd arm, respectively (Facon, 2019, Mateos, 2018). Isatuximab is an anti-CD38 mAb approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone to treat relapsed/refractory MM. The drug has also shown clinical responses as combination therapy to treat NDMM (Trudel, 2019). Corticosteroids have been the backbone of most myeloma-targeted therapies since the discovery of their effectiveness. Due to the continuous treatment paradigm, the cumulative dose of corticosteroids in patients is substantial. Steroids inflict reduction in both short- and long-term quality of life and increase patients' receptiveness to infections. Infections are one of the main reasons for complications and death during active first line treatment and the rate rises with age (Mothy, 2019). Instead of reducing or removing corticosteroids, isatuximab will replace corticosteroids to evaluate the effectiveness and safety of the novel regime of isatuximab-bortezomib-lenalidomide. Aim: The study will evaluate isatuximab (Isa) in combination with bortezomib (V) and lenalidomide (R) with minimal dexamethasone (d) as first-line treatment in transplant-ineligible patients. The primary endpoint is the number of patients who achieve measurable residual disease negative (Euroflow NGF 10 -5) complete response during and/or after 18 cycles of study treatment. Secondary endpoints include progression free survival, overall survival, overall response rate, safety evaluations and patient-reported outcome. Methods: The REST study is an academic, single arm, open-label, phase 2 study of NDMM patients ineligible for ASCT. 51 patients are included and receive Isa-VRd (Isa: 10 mg/kg IV Days 1, 8, 15, 22 during cycle 1, Q2W cycle 2-18; V: 1, 3 mg/m 2 SC Days 1, 8, 15 during cycle 1-8; R: 25 mg PO Days 1-21 during all cycles; d: 20 mg PO Days 1, 8, 15, 22 only for the first 2 cycles), all 28-day cycles. Results: Recruitment was completed in January 2023. Baseline characteristics, safety summary and preliminary results can be found in Table 1. The median age is 77 years, range 70-88 years. Twenty-nine patients developed 60 grade >3 non-hematological adverse events (AE), including infections (n=26), syncope (n=5), diarrhea (n=4), skeletal pain (n=4), arrhythmias (n=3), acute renal failure (n=3), increased transaminases (n=3), venous thromboembolism (n=2), arthritis (n=2), gastrointestinal hemorrhage (n=2), peripheral sensory neuropathy (n=2), edema (n=1), hyperglycemia (n=1), rash (n=1) and opiate intoxication (n=1). At a median follow up of 12 months, the ORR was 100% (51/51) with very good partial response or better at80.3% (41/51). Forty-four patients are still on study. One patient died from septicemia with staphylococcus aureus, four patients discontinued due to disease progression, one patient due to poor compliance and one patients for safety reasons judged by the investigator. Conclusions: Isa-VRd in the transplant ineligible population with a median age of 77 years has a tolerable safety profile. Isa-VRd is showing encouraging preliminary efficacy in NDMM ineligible for transplant. Follow-up is ongoing. Acknowledgements: Sanofi funded this research.

The possibility of osteoporosis and avascular necrosis caused by the COVID-19 pandemic. Analysis of literature

The SARS-CoV-2 (COVID-19) coronavirus pandemic has prompted scientific research. Hypotheses regarding its pathogeneticmechanisms and treatment are formulated, unwanted consequences of the infection are determined. Objective. To provideuseful information for clinicians about possible complications from the musculoskeletal system after COVID-19 for thetimely application of effective methods of their prevention. Materials: Electronic databases PMC, PubMed and Scopus wereused to search for the sources of information published from December 2019 to December 2021. The full text of the articleswas reviewed to confirm their relevance to the stated purpose of the review. Results. Patients after a severe course of SARSCoV-2 have a high risk of complications such as osteoporosis and avascular osteonecrosis due to a number of reasons. It isnoted that hypocalcemia is considered as an indicator of the severity and progression of the course of COVID-19. Vitamin Ddeficiency increases the risk of contracting COVID-19 and is associated with increased severity and mortality from the infection.Decreased proliferation and differentiation of osteoblasts can provoke elevated levels of cytokines under cytokine stormconditions. Hypoxia caused by SARS-CoV-2 is an important factor in increasing the differentiation and activity of osteoclastsand, accordingly, increasing osteoresorption. The relationship between the development of avascular osteonecrosis and longterm use of high doses of corticosteroids in patients with severe acute respiratory syndrome has been established. Conclusions. Research of musculoskeletal complications after COVID-19 is ongoing for correct forecasting and effective prevention. The use of corticosteroids in the treatment of patients with COVID-19 should be considered. It is necessary to pay attention to the diagnosis of osteoporosis, since there are many risk factors for increased bone fragility in hospitalized patients. Patients suffering from the effects of COVID-19 will need a comprehensive recovery and rehabilitation treatment plan

P888: REPLACING STEROIDS IN TRANSPLANT-INELIGIBLE MULTIPLE MYELOMA: THE PHASE 2 ISATUXIMAB-BORTEZOMIB-LENALIDOMIDE-DEXAMETHASONE REST STUDY

Background: Standard therapies for newly diagnosed multiple myeloma (NDMM) patient’s ineligible for autologous stem-cell transplantation (ASCT) have been lenalidomide-dexamethasone (Rd), bortezomib-lenalidomide-dexamethasone (VRd) or bortezomib-melphalan-prednisone (VMP). The benefit of adding an anti-CD 38 monoclonal antibody (mAb) to the standard treatments of VMP and Rd has been demonstrated in two large phase 3 studies (Facon, 2019. Mateos, 2018). Isatuximab is an anti-CD38 mAb approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone to treat relapsed/refractory MM, and has also shown clinical responses as combination therapy to treat NDMM (Trudel, 2019). Corticosteroids have been the backbone of most myeloma targeted therapies since the discovery of their effectiveness. Due to the continuous treatment paradigm, the cumulative dose of corticosteroids in patients is substantial. Steroids inflict reduction in both short- and long-term quality of life and increase patients’ receptiveness for infections. Infections are one of the main reasons for complications and death during active first line treatment, and the rate rises with age. Both steroid-free regimens and regimens with reduced corticosteroids have demonstrated improved safety and similar efficacy as regimens containing steroids. Aims: The study will evaluate isatuximab (Isa) in combination with bortezomib (V) and lenalidomide (R) with minimal dexamethasone (d) as first-line treatment in transplant-ineligible patients. The primary endpoint is the number of patients who achieve measurable residual disease negative (Euroflow NGF 10-5) complete response during and/or after 18 cycles of study treatment. Secondary endpoints include progression free survival, overall survival, overall response rate (ORR), safety evaluations and patient-reported outcome. Methods: The REST study is an academic, single arm, open-label, phase 2 study of NDMM patients ineligible for ASCT. 50 patients will be included and receive Isa-VRd (Isa:10 mg/kg IV Days 1, 8, 15, 22 during cycle 1, QW cycle 2-18; V: 1,3 mg/m2 SC Days 1,8,15 during cycle 1-8; R: 25 mg PO Days 1-21 during all cycles; d: 20 mg PO Days 1,8,15,22 only for the first 2 cycles), all 28-day cycles. Results: As of January 31, 2022, 17 patients have been enrolled. Baseline characteristics can be found in Table 1. At data-cutoff, the median number of cycles started by patients was 3.6 (range 1-8) and the median duration of exposure was 16 (range 3-28) weeks. 8 patients developed 14 grade ≥3 non-hematological adverse eventd (AE), including infections (n=7), fever (n=1), skeletal pain (n=2), acute renal failure (n=1), peripheral sensory neuropathy (n=1), diarrhea (n=1) edema (n=1). There were no AEs leading to definitive treatment discontinuation. At a follow up of 6 months, the ORR was 100% (15/15) and the ≥very good partial response rate was 53.3% (8/15 patients). Image:Summary/Conclusion: Isa-VRd in the transplant ineligible population has a tolerable safety profile. Isa-VRd is showing encouraging preliminary efficacy in NDMM ineligible for transplant. Enrollment and follow-up is ongoing. Acknowledgements: Sanofi sponsors the REST study.

Using biomarkers to adjust corticosteroid dose in patients with severe asthma.

Use of biomarkers may help reduce inhaled corticosteroid burden in severe asthma if treatment advice is followed. T2 low asthma is less common than previously thought. https://bit.ly/3rG7SZ2

Composite type-2 biomarker strategy versus a symptom–risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial

SummaryBackgroundAsthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide [FENO], blood eosinophils, and serum periostin) with a standardised symptom–risk-based algorithm (control).MethodsWe did a single-blind, parallel group, randomised controlled trial in adults (18–80 years of age) with severe asthma (at treatment steps 4 and 5 of the Global Initiative for Asthma) and FENO of less than 45 parts per billion at 12 specialist severe asthma centres across England, Scotland, and Northern Ireland. Patients were randomly assigned (4:1) to either the biomarker strategy group or the control group by an online electronic case-report form, in blocks of ten, stratified by asthma control and use of rescue systemic steroids in the previous year. Patients were masked to study group allocation throughout the entirety of the study. Patients attended clinic every 8 weeks, with treatment adjustment following automated treatment-group-specific algorithms: those in the biomarker strategy group received a default advisory to maintain treatment and those in the control group had their treatment adjusted according to the steps indicated by the trial algorithm. The primary outcome was the proportion of patients with corticosteroid dose reduction at week 48, in the intention-to-treat (ITT) population. Secondary outcomes were inhaled corticosteroid (ICS) dose at the end of the study; cumulative dose of ICS during the study; proportion of patients on maintenance oral corticosteroids (OCS) at study end; rate of protocol-defined severe exacerbations per patient year; time to first severe exacerbation; number of hospital admissions for asthma; changes in lung function, Asthma Control Questionnaire-7 score, Asthma Quality of Life Questionnaire score, and T2 biomarkers from baseline to week 48; and whether patients declined to progress to OCS. A secondary aim of our study was to establish the proportion of patients with severe asthma in whom T2 biomarkers remained low when corticosteroid therapy was decreased to a minimum ICS dose. This study is registered with ClinicalTrials.gov, NCT02717689 and has been completed.FindingsPatients were recruited from Jan 8, 2016, to July 12, 2018. Of 549 patients assessed, 301 patients were included in the ITT population and were randomly assigned to the biomarker strategy group (n=240) or to the control group (n=61). 28·4% of patients in the biomarker strategy group were on a lower corticosteroid dose at week 48 compared with 18·5% of patients in the control group (adjusted odds ratio [aOR] 1·71 [95% CI 0·80–3·63]; p=0·17). In the per-protocol (PP) population (n=121), a significantly greater proportion of patients were on a lower corticosteroid dose at week 48 in the biomarker strategy group (30·7% of patients) compared with the control group (5·0% of patients; aOR 11·48 [95% CI 1·35–97·83]; p=0·026). Patient choice to not follow treatment advice was the principle reason for loss to PP analysis. There was no difference in secondary outcomes between study groups and no loss of asthma control among patients in the biomarker strategy group who reduced their corticosteroid dose.InterpretationBiomarker-based corticosteroid adjustment did not result in a greater proportion of patients reducing corticosteroid dose versus control. Understanding the reasons for patients not following treatment advice in both treatment strategies is an important area for future research. The prevalence of T2 biomarker-low severe asthma was low.FundingThis study was funded, in part, by the Medical Research Council UK.

Effect of fixed-dose subcutaneous reslizumab on asthma exacerbations in patients with severe uncontrolled asthma and corticosteroid sparing in patients with oral corticosteroid-dependent asthma: results from two phase 3, randomised, double-blind, placebo-controlled trials

Reslizumab 3 mg/kg administered intravenously is approved for the treatment of severe eosinophilic asthma. We assessed the safety and efficacy of subcutaneous reslizumab 110 mg in two trials in patients with uncontrolled severe asthma and increased blood eosinophils. The aim was to establish whether subcutaneous reslizumab 110 mg can reduce exacerbation rates in these patients (study 1) or reduce maintenance oral corticosteroid dose in patients with corticosteroid-dependent asthma (study 2). Both studies were randomised, double-blind, placebo-controlled, phase 3 studies. Entry criteria for study 1 were uncontrolled severe asthma, two or more asthma exacerbations in the previous year, a blood eosinophil count of 300 cells per μL or more (including no more than 30% patients with an eosinophil count <400 cells/μL), and at least a medium dose of inhaled corticosteroids with one or more additional asthma controllers. Patients in study 2 had severe asthma, a blood eosinophil count of 300 cells per μL or more, daily maintenance oral corticosteroid (prednisone 5-40 mg, or equivalent), and high-dose inhaled corticosteroids plus another controller. Patients were randomly assigned (1:1) to subcutaneous reslizumab (110 mg) or placebo once every 4 weeks for 52 weeks in study 1 and 24 weeks in study 2. Patients and investigators were masked to treatment assignment. Primary efficacy outcomes were frequency of exacerbations during 52 weeks in study 1 and categorised percentage reduction in daily oral corticosteroid dose from baseline to weeks 20-24 in study 2. Primary efficacy analyses were by intention to treat, and safety analyses included all patients who received at least one dose of study treatment. These studies are registered with ClinicalTrials.gov, NCT02452190 (study 1) and NCT02501629 (study 2). Between Aug 12, 2015, and Jan 31, 2018, 468 patients in study 1 were randomly assigned to placebo (n=232) or subcutaneous reslizumab (n=236), and 177 in study 2 to placebo (n=89) or subcutaneous reslizumab (n=88). In study 1, we found no significant difference in the exacerbation rate between reslizumab and placebo in the intention-to-treat population (rate ratio 0·79, 95% CI 0·56-1·12; p=0·19). Subcutaneous reslizumab reduced exacerbation frequency compared with placebo in the subgroup of patients with blood eosinophil counts of 400 cells per μL or more (0·64, 95% CI 0·43-0·95). Greater reductions in annual exacerbation risk (p=0·0035) and longer time to first exacerbation were observed for patients with higher trough serum reslizumab concentrations. In study 2, we found no difference between placebo and fixed-dose subcutaneous reslizumab in categorised percentage reduction in daily oral corticosteroid dose (odds ratio for a lower category of oral corticosteroid use in the reslizumab group vs the placebo group, 1·23, 95% CI 0·70-2·16; p=0·47). The frequency of adverse events and serious adverse events with reslizumab were similar to those with placebo in both studies. Fixed-dose (110 mg) subcutaneous reslizumab was not effective in reducing exacerbation frequency in patients with uncontrolled asthma and increased blood eosinophils (≥300 cells/μL), or in reducing the daily maintenance oral corticosteroid dose in patients with oral corticosteroid-dependent severe eosinophilic asthma. Higher exposures than those observed with 110 mg subcutaneous reslizumab are required to achieve maximal efficacy. Teva Branded Pharmaceutical Products R&D.

Evaluation of low-dose glucocorticoid regimen in association with cyclophosphamide in patients with glomerulonephritis.

The treatment of most glomerulonephritides is still based on a combination of an oral corticosteroid and an alkylating agent, with favorable outcomes, but with serious side effects. The objective of this study was to reduce the cumulative corticosteroid dose in patients with high risk of corticosteroid-related adverse events by replacing daily oral corticosteroids with intravenous (iv) methylprednisolone pulses, associated with monthly pulse i.v. cyclophosphamide (according to KDIGO guidelines) in patients with glomerulonephritis. This was a retrospective cohort study conducted at a single nephrology centre. In the course of a 6-month run-in phase, all the patients received non-immunosuppressive pathogenic treatment. High-risk patients, who still had urinary protein excretion of at least 3.5g per day at the end of these 6months, received a combination of corticosteroids and cyclophosphamide. Patients were divided in two groups: group 1 (23 patients)-included patients with high risk of corticosteroid-related adverse events received monthly methylprednisolone 1g/day, 3days and i.v. cyclophosphamide for 6months, and group 2 (84 patients)-received oral corticosteroids (as per KDIGO recommended dose) and i.v. cyclophosphamide. The primary outcome-time to a combined end-point of doubling of serum creatinine, ESRD, need for chronic renal replacement therapy or death; secondary outcomes: complete remission [proteinuria < 0.3g per 24h (urinary protein-creatinine rate < 300mg/g [< 30mg/mmol]]; partial remission (proteinuria > 0.3 but < 3.5g per 24h or a decrease in proteinuria by at least 50% from the initial value) and adverse events. At 6months, there was no difference in the primary composite end-point: 8.7% patients from the group 1 and 20.2% patients from the group 2 (P = 0.199) reached this end-point. Similar data were also recorded at 12months. Secondary end-points were also similar between treatment groups. More patients receiving oral corticosteroids experienced infections, but without statistical significance. Our data indicate that low i.v. dose corticosteroids and cyclophosphamide administered monthly in patients with high risk of corticosteroid-related adverse events and primary glomerulonephritis are equally effective, with fewer metabolic disorders and infections.

Tiotropium in asthma: From bench to bedside.

Tiotropium is a long-acting muscarinic antagonist approved for maintenance treatment of asthma in children, adolescents, and adults in the United States, and recommended as add-on treatment for uncontrolled asthma despite treatment with inhaled corticosteroids and/or long-acting beta-2 agonists. This review traces the journey of tiotropium from its historical origins through early preclinical testing to human clinical trials and real-life studies. A search was performed in PubMed using search terms 'tiotropium' and 'asthma.' Relevant references cited in those articles were reviewed. English language articles published from December 2008-December 2018 were screened. Articles evaluating the efficacy, cost-effectiveness, real-life evidence, and steroid-sparing effect of tiotropium with inadequately controlled asthma were included. Anticholinergics have a long history of use in the treatment of obstructive airway diseases. Evidence indicates that tiotropium's mechanism of action consists of bronchodilation and diminished mucus secretion, with preclinical evidence suggesting an anti-inflammatory effect as well. Phase 2 and 3 clinical trials have demonstrated that tiotropium is efficacious and safe, resulting in significant improvements in lung function in adults, adolescents, and children across asthma severities. Emerging evidence suggests that add-on tiotropium might potentially enable reductions in inhaled corticosteroid dose in patients with uncontrolled asthma. Further, tiotropium is a cost-effective treatment option that is also effective in the clinical practice setting. An increasing body of evidence indicates that tiotropium can play a significant role in the treatment of patients with uncontrolled asthma.

Clinical efficacy of implementing Bio Immune(G)ene MEDicine in the treatment of chronic asthma with the objective of reducing or removing effectively corticosteroid therapy: A novel approach and promising results.

Asthma is one of the diseases that demonstrates a wide range of variation in its clinical expression, in addition to an important heterogeneity in the pathophysiological mechanisms present in each case. The ever-increasing knowledge of the molecular signalling routes and the development of the Bio Immune(G)ene Medicine [BI(G)MED] therapy in line with this knowledge has revealed a whole novel potential set of self-regulation biological molecules, that may be used to promote the physiological immunogenic self-regulation mechanisms and re-establish the homeostatic balance at a genomic, proteomic and cellular level. The aim of the present study is to demonstrate that the sublingual use of a therapeutic protocol based on BI(G)MED regulatory BIMUREGs in the treatment of chronic asthma may reduce or suppress corticosteroid therapy and avoid its harmful side effects which some patients suffer when using this treatment on a long-term basis. The clinical efficacy of BI(G)MED for chronic asthma was evaluated through a multi-centre study carried out in 2016 implementing a 6-month BI(G)MED treatment protocol for Bronchial Asthma. A total of 61 patients from private medical centres and of European countries including Germany, Austria, France, Belgium and Spain participated. The manuscript describes in detail the clinical efficacy of Bio Immune(G)ene regulatory BI(G)MED treatment protocol that allows the reduction or total removal of the corticosteroid dose in patients with chronic asthma. No adverse reactions were observed. The BI(G)MED regulatory therapy brings novel therapeutic possibilities as an effective and safe treatment of chronic asthma. BI(G)MED was demonstrated to significantly reduce asthma severity when parameter compositions were all analysed by categorical outcomes. Therefore, it is considered a good therapeutic alternative for patients who respond poorly to steroids.

Rituximab in pemphigus.

Pemphigus is a severe autoimmune blistering disease mediated by pathogenic anti-desmoglein antibodies leading to an inter keratinocyte disjunction. Rituximab is a monoclonal antibody that binds to the CD-20 antigen of B lymphocytes, which causes B-cell depletion and a subsequent reduction in pathogenic autoantibodies. Its therapeutic role in pemphigus has been progressively growing with increasing evidence of successful outcomes. Rituximab was initially off-labeled used as an alternative in patients with recalcitrant or relapsing pemphigus and in patients with contraindications to systemic corticosteroids. Recently, a large randomized clinical trial has shown that first-line use of rituximab combined with short-term prednisone regimen was both more effective and potentially safer than a standard regimen of high doses of corticosteroids in patients with moderate to severe pemphigus.

High doses of systemic corticosteroids in patients hospitalized for exacerbation of chronic obstructive pulmonary disease. A cohort study

ObjectivesTo assess the effect of high doses of corticosteroids in patients hospitalized for exacerbation of chronic obstructive pulmonary disease (COPD). Patients and methodsA prospective cohort study was conducted on patients hospitalized with COPD between January and March 2015, grouped according to the glucocorticoid dosage administered (cutoff, 40mg of prednisone/day). We compared the results of hospital stay, readmission and mortality at 3 months of discharge. ResultsWe analyzed 87 patients. The median daily dose was 60mg of prednisone (interquartile range, 46.67–82.33mg/day), and the administration route was intravenous in 96.6% of the cases. We established a relative risk (RR) for hospital stays longer than 8 days of 1.095 (95% CI 0.597–2.007; p=.765) when steroid dosages greater than 40mg/day were employed. In these patients, the hazard ratio (HR) for readmission in the 3 months after discharge was 0.903 (95% CI 0.392–2.082; p=.811), and the mortality was 1.832 (95% CI 0.229–16.645; p=.568). Neither the RR nor the HR varied in a statistically significant manner after adjusting for confounding factors. ConclusionsA daily dose greater than 40mg of prednisone in patients hospitalized for COPD exacerbation was not associated with a shorter hospital stay or a reduction in readmissions or mortality at 3 months.

Dosis altas de corticoides sistémicos en pacientes ingresados por exacerbación de enfermedad pulmonar obstructiva crónica. Un estudio de cohortes

ObjectivesTo assess the effect of high doses of corticosteroids in patients hospitalised for exacerbation of chronic obstructive pulmonary disease (COPD). Patients and methodsA prospective cohort study was conducted on patients hospitalized with COPD between January and March 2015, grouped according to the glucocorticoid dosage administered (cutoff, 40mg of prednisone/day). We compared the results of hospital stay, readmission and mortality at 3 months of discharge. ResultsWe analysed 87 patients. The median daily dose was 60mg of prednisone (interquartile range, 46.67-82.33mg/day), and the administration route was intravenous in 96.6% of the cases. We established a relative risk (RR) for hospital stays longer than 8 days of 1.095 (95% CI 0.597-2.007; P=.765) when steroid dosages greater than 40mg/day were employed. In these patients, the hazard ratio (HR) for readmission in the 3 months after discharge was 0.903 (95% CI 0.392-2.082; P=.811), and the mortality was 1.832 (95% CI 0.229-16.645; P=.568). Neither the RR nor the HR varied in a statistically significant manner after adjusting for confounding factors. ConclusionsA daily dose greater than 40mg of prednisone in patients hospitalised for COPD exacerbation was not associated with a shorter hospital stay or a reduction in readmissions or mortality at 3 months.

The safety of mepolizumab for the treatment of asthma

ABSTRACTIntroduction: Asthma is an airway disease characterized by airway inflammation. It is associated with significant morbidity, mortality, and costs to the healthcare system and society. Interleukin-5 (IL-5) was identified for its role in eosinophil development, maturation, and survival in tissues, which has been related to disease severity and airway eosinophilia.Areas covered: In this review, we will present the pharmacokinetics and dynamics of mepolizumab in addition to efficacy and safety data.Expert Opinion: Mepolizumab is novel, new, first-in-class therapy targeting IL-5. It has been found to be particularly effective in the management of patients with asthma whose peripheral blood eosinophil count is at a well-defined cut point within the normative range. This easily available biomarker, along with a history of asthma exacerbations, has translated into a clinically significant reduction in asthma exacerbations and the dose of oral corticosteroids in patients who previously have been prednisone-dependent. The pivotal studies indicate that mepolizumab was well tolerated, with the most frequently reported adverse events being headache, nasopharyngitis, worsening of asthma, and local injection reactions. These study investigators did not report any deaths or anaphylaxis related to mepolizumab.

AB0563 Relationship between Readmission and Corticosteroid Doses in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

BackgroundAlthough corticosteroid treatment is essential in the management of rheumatic diseases, adverse events of corticosteroids pose serious problems. Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) frequently requires higher corticosteroids doses than does...

Adalimumab for steroid sparing in patients with giant-cell arteritis: results of a multicentre randomised controlled trial

ObjectivesTo evaluate the effect of adding a 10-week treatment of adalimumab to a standardised treatment with corticosteroids on the ability to taper more rapidly corticosteroid doses in patients with newly...

SAT0161 The Role of Biological Agents in the Management of Large Vessel Vasculitis (LVV): A Systematic Review

BackgroundLarge vessel vasculitis (LVV) includes two major variants with similar histopathology - giant cell arteritis (GCA) and Takayasu’s arteritis (TAA). High dose glucocorticoids are the mainstay for treatment; however, many...

Randomised, double-blind, placebo-controlled study of tacrolimus in myasthenia gravis

ObjectivesTo evaluate the ability of tacrolimus to reduce the corticosteroid dose in patients with myasthenia gravis (MG) and the drug's safety in a double-blind, placebo-controlled, parallel group study.MethodsPatients being treated...

Combination Therapy with Budesonide and Formoterol in Single Inhaler of Asthma

Inhaled corticosteroids are the mainstay of asthma therapy, but there is now compelling evidence that addition of a long-acting inhaled β2-agonist, such as formoterol, gives better control in terms of reduced symptoms, improved lung function and reduced exacerbations in patients with mild to severe persistent asthma than increasing the dose of corticosteroids in patients not fully in control by low dose. This has led to development of fixed dose combination inhalers such as budesonide/formoterol. Budesonide/formoterol combination in a single inhaler represents a safe, effective and convenient treatment option for management of patients with unstable asthma than inhaled steroid alone. This combination has shown effectiveness for both maintenance and rescue therapy. Clinical results show that the budesonide/formoterol by SMART approach prolongs the time to first severe asthma exacerbation, reduces frequency of exacerbation and maintains day to day asthma control at a reduced corticosteroid load and cost when compared with higher fixed maintenance dose of combination inhalers. With regular maintenance therapy by this approach it is more likely to improve patient compliance. Budesonide/formoterol combination inhaler has shown to have a faster bronchodialatory effect compared with other combination inhalers, a quality highly in demand during exacerbation episodes. Due to this rapid onset of action, budsonide/formoterol in a single inhaler lends itself to be used as a rescue medication, as well.

Requirement of Perioperative Stress Doses of Corticosteroids

To determine the requirement for perioperative supplemental (stress) doses of corticosteroids in patients receiving long-term corticosteroid therapy and undergoing a surgical procedure. Corticosteroids are among the most commonly prescribed medications and will predictably result in suppression of the hypothalamic-pituitary-adrenal axis with long-term use. Patients receiving therapeutic dosages of corticosteroids frequently require surgery; these patients are almost universally treated with stress doses of corticosteroids during the perioperative period. MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. Randomized controlled trials (RCTs) comparing stress doses of corticosteroids with placebo and cohort studies that followed up patients after surgery in which perioperative stress doses of corticosteroids were not administered. Data were abstracted on the study design, study size, study setting, patient population, dosage and duration of previous corticosteroid therapy, adrenal function testing results, surgical intervention, corticosteroid dosing regimen, intraoperative and postoperative hemodynamic profile, and incidence of adrenal crisis. Nine studies met our inclusion criteria, including 2 RCTs and 7 cohort studies. These studies enrolled a total of 315 patients who underwent 389 surgical procedures. In the 2 RCTs, there was no difference in the hemodynamic profile between patients receiving stress doses of corticosteroids compared with patients receiving only their usual daily dose of corticosteroid. In the 5 cohort studies in which patients continued to receive their usual daily dose of corticosteroid without the addition of stress doses, no patient developed unexplained hypotension or adrenal crisis. One patient in each of the 2 cohort studies (5% and 1% of the cohort) in which the usual daily dose of corticosteroid was stopped 48 and 36 hours before surgery developed unexplained hypotension; both of these patients responded to hydrocortisone and fluid administration. Patients receiving therapeutic doses of corticosteroids who undergo a surgical procedure do not routinely require stress doses of corticosteroids so long as they continue to receive their usual daily dose of corticosteroid. Adrenal function testing is not required in these patients because the test is overly sensitive and does not predict which patient will develop an adrenal crisis. Patients receiving physiologic replacement doses of corticosteroids owing to primary disease of the hypothalamic-pituitary-adrenal axis, however, require supplemental doses of corticosteroids in the perioperative period.

Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double-blind randomised study

Th2 cytokines play an important part in the pathogenesis of asthma. Our aim was to study the effect of suplatast tosilate, a selective Th2 cytokine inhibitor, on asthma control and asthma exacerbations during reduction of inhaled corticosteroid dose in patients with steroid-dependent asthma. 85 patients with moderate to severe asthma taking high doses (> or = 1500 microg per day) of inhaled beclometasone dipropionate, were assigned suplatast tosilate (100 mg three times daily) or placebo for 8 weeks in a double-blind, randomised, parallel-group, multicentre trial. During the first 4 weeks, other medications remained unchanged (add-on phase); during the next 4 weeks, the doses of beclometasone were halved (steroid-reduction phase). Main outcome measures were pulmonary function, asthma symptoms, and use of beta2-agonists. Data were available from 77 patients. During the add-on phase, suplatast tosilate treatment, compared with placebo, was associated with higher forced expiratory volume in 1 s (mean difference between groups for changes from baseline at week 4, 0.20 L [95% CI 0.16-0.24], p=0.043), morning peak expiratory flow (18.6 L/min [14.1-23.1], p=0.037), and less diurnal variation in peak expiratory flow rate, asthma symptom scores (7.1 [6.6-7.6], p=0.029), and serum concentrations of eosinophil cationic protein and IgE. In the steroid-reduction phase, pulmonary function, asthma symptoms, and use of beta2-agonist deteriorated significantly more in the placebo group than in the suplatast group. Treatment with a Th2 cytokine inhibitor in steroid-dependent asthma improves pulmonary function and symptom control, and allows a decrease in dose of inhaled corticosteroid without significant side-effects. Some improvements in pharmacokinetics are, however, needed.