Reduction In Corticosteroid Use Research Articles

Corticosteroid Use and Adherence in Patients Treated with Acthar Gel for Advanced Sarcoidosis.

Long-term corticosteroid use in immune-mediated diseases is associated with increased risk of adverse events (AEs) and worsened health-related quality of life (HRQoL). Previous studies report chronic high-dose corticosteroid therapy results in higher rates of healthcare resource use and AE-related medical costs. Recent studies suggest Acthar® Gel (repository corticotropin injection) is an effective steroid-sparing therapy for sarcoidosis. This study compares the corticosteroid-sparing effect between Acthar Gel and comparators and evaluates the impact of Acthar Gel adherence on reduction of corticosteroid burden. A retrospective analysis of a large administrative pharmacy and medical claims database (Symphony Health Solutions) was conducted. Patients were included with confirmed ICD-9/10 diagnosis for sarcoidosis in the study period (2014-2020), followed by ≥ 2 Acthar Gel claims or comparators (janus kinase inhibitor (JAKi)/rituximab), ≥ 18years old, with 12months coverage pre/post index. Outcomes were compared as change from baseline. Acthar Gel adherence was determined by proportion of days covered in the follow-up period. The Acthar Gel (n = 735) and comparator (n = 626) cohorts were mostly female (68-72%) between 55 and 58years old. Compared to the comparator cohort at baseline, Acthar Gel patients had greater any corticosteroid use (80% vs. 56%, p < 0.001), extended use (61% vs. 32%, p < 0.001), and mean average daily dose (6.72 vs. 3.03, p < 0.001). After treatment, Acthar Gel patients had greater reduction from baseline in any corticosteroid use (-9.0% vs. -3.2%) and extended use (-10.0% vs. -3.0%). In the Acthar Gel adherence cohorts, patients with above average adherence had greater reduction in both measures (-11.2% vs. -6.1%; -11.6% vs. -7.6%, respectively) than patients with below average adherence. Acthar Gel patients had greater reduction of extended use at all dose levels. Acthar Gel is associated with reductions in corticosteroid use compared to alternatives. Better adherence is associated with greater reduction in corticosteroid exposure. Key Summary Points.

Bevacizumab for the Treatment of Patients With Brain Radionecrosis

&#x0D; This review identified limited evidence regarding the clinical effectiveness and safety of bevacizumab for patients with symptomatic brain radionecrosis after radiosurgery. These identified studies had several limitations, most notably due to the limited number of studies with control groups; therefore, the findings related to the effectiveness and safety in this population are uncertain.&#x0D; For adult patients with symptomatic brain radionecrosis, treatment with bevacizumab may be associated with radiographic responses, a reduction in volumetric outcomes, an improvement in overall clinical and neurologic symptoms, an improvement in functional outcomes, and a reduction in corticosteroid use.&#x0D; Limited evidence from 1 study suggests that treatment with bevacizumab may be associated with greater radiographic response, a reduction in volumetric outcomes, and clinical symptom improvement compared to treatment with corticosteroids. The recurrence of brain radionecrosis for patients who received bevacizumab compared to corticosteroids was similar between groups.&#x0D; Commonly reported adverse events after patients with symptomatic brain radionecrosis were treated with bevacizumab included hypertension, proteinuria, edema, pulmonary embolism, and various thromboembolic events.&#x0D;

Real-world analysis of outcomes of patients receiving bevacizumab for recurrent glioblastoma in British Columbia.

e14017 Background: Bevacizumab (Bev) has been publicly funded in British Columbia (BC) since 2011 for treatment of recurrent glioblastoma (rGBM). We performed a retrospective outcomes assessment of patients with rGBM treated with Bev to evaluate treatment practices and outcomes. Methods: Patients with rGBM treated at BC Cancer centers with Bev between January 2011 and December 2017 were reviewed. Patient demographics, tumor characteristics, treatment regimens, and dates of radiographic progression and death were collected. Kaplan-Meier method was used to assess survival, and comparisons were made using the log-rank test. Results: 182 patients were reviewed. There were 180 reported deaths with median PFS 3 months (CI95 = 2.5 - 3.5) and OS 7 months (CI95 = 6.2-7.8) from Bev initiation. Higher corticosteroid dose prior to Bev initiation was associated with worse OS on univariate and multivariate analysis ( p = 0.40 and 0.01, respectively). 67% of patients on corticosteroids reduced their dose shortly after Bev initiation. Most patients (68%) were treated with multiple lines of therapy prior to Bev, with a median time from chemoradiation to Bev initiation of 8 months (range 1-67). Patients started on Bev &lt; 6 months from completion of chemoradiation (prior to adjuvant temozolomide completion) had improved PFS ( p = 0.02) and OS compared to those who started Bev later ( p = 0.05), but there was no association between extent of treatment prior to Bev and outcomes ( p = 0.09). Addition of chemotherapy to Bev did not improve survival over Bev monotherapy ( p = 0.10). Conclusions: Bev combinations with chemotherapy did not confer survival advantage over Bev monotherapy. Furthermore, our results show that patients receiving Bev before completion of adjuvant chemotherapy have better outcomes, suggesting pseudoprogression may have prompted the therapeutic switch. Despite limited benefits to overall survival, Bev is associated with reduction in corticosteroid use and likely improvement in quality of life. Therefore, further research is required to optimize patient selection for and administration of Bev. Additional analysis of rGBM patients prescribed Bev until 2020 in BC is currently underway.

Resilience-based Integrated IBD Care Is Associated With Reductions in Health Care Use and Opioids

Integrated inflammatory bowel disease (IBD) care is effective but not routinely implemented. Validated methods that simultaneously address mind and body targets such as resilience may improve access and outcomes. We describe the development and implementation of the GRITT method and its impact on resilience, health care utilization (HCU), and opioid use in IBD. Consecutive patients from an academic IBD center were evaluated for low resilience on the basis of provider referral. Low resilience patients were invited to participate in the GRITT program. Primary outcome was % reduction in HCU. Secondary outcomes were change in resilience and corticosteroid and opioid use. Patients were allocated into 2 groups for analysis: GRITT participants (GP) and non-participants (NP). Clinical data and HCU in the year before enrollment were collected at baseline and 12 months. One-way repeated measures multivariate analysis of covariance evaluated group× time interactions for the primary outcome. Effect size was calculated for changes in resilience over time. Of 456 screened IBD patients 394 were eligible, 184 GP and 210 NP. GP had greater reduction in HCU than NP: 71% reduction in emergency department visits, 94% reduction in unplanned hospitalizations. There was 49% reduction in opioid use and 73% reduction in corticosteroid use in GP. Resilience increased by 27.3 points (59%), yielding a large effect size (d= 2.4). Mind-body care that focuses on building resilience in the context of IBD care may be a novel approach to reduce unplanned HCU and opioid use, but large, multicenter, randomized controlled trials are needed.

NCOG-24. REAL-WORLD ANALYSIS OF OUTCOMES OF PATIENTS RECEIVING BEVACIZUMAB FOR RECURRENT GLIOBLASTOMA IN BRITISH COLUMBIA

Abstract BACKGROUND Bevacizumab (Bev) has been publicly funded in British Columbia (BC) since 2011 for treatment of recurrent glioblastoma (rGBM). We performed a retrospective outcomes assessment of patients with rGBM treated with Bev. METHODS Patients with rGBM treated at BC Cancer centers with Bev between January 2011 and December 2016 were reviewed. Patient demographics, tumor characteristics, treatment regimens, and dates of radiographic progression and death were collected. Kaplan-Meier method was used to assess survival, and comparisons were made using the log-rank test. RESULTS 138 patients were reviewed. There were 136 reported deaths with median PFS 3 months (CI95 = 2.5 - 3.5) and OS 7 months (CI95 = 6.1-8.0) from Bev initiation. 64% of patients on corticosteroids prior to Bev reduced their dose shortly after initiation. The majority of patients (72%) were treated with multiple lines of therapy prior to Bev, with a median time from chemoradiation to Bev initiation of 8 months (range 1-67). Patients started on Bev &amp;lt; 6 months from chemoradiation (prior to completion of adjuvant temozolomide) had improved OS compared to those who started Bev later (p = 0.05), but there was no association between extent of treatment prior to Bev and outcomes (p = 0.182). Addition of chemotherapy to Bev did not improve survival over Bev monotherapy (p = 0.175). CONCLUSIONS Despite limited benefits to overall survival, Bev is associated with reduction in corticosteroid use and likely improvement in quality of life. Bev combinations with chemotherapy did not confer survival advantage over Bev monotherapy. Furthermore, our results show that patients receiving Bev before completion of adjuvant chemotherapy have better outcomes, suggesting pseudoprogression may have prompted the therapeutic switch. Further research is required to optimize patient selection for and administration of Bev. Additional analysis of rGBM patients prescribed Bev until 2020 in BC is currently underway.

Reduced Systemic Corticosteroid Use among Pediatric Patients With Inflammatory Bowel Disease in a Large Learning Health System.

Corticosteroids have long been used to treat inflammatory bowel disease. However, cumulative corticosteroid exposure is associated with adverse effects, particularly in growing children. Professional guidelines recommend steroid-sparing strategies. It remains unknown whether corticosteroid use has decreased in children with inflammatory bowel disease. We performed retrospective cohort study using data from 2007 to 2018 from the international multi-center ImproveCareNow Network, a pediatric inflammatory bowel disease quality improvement collaborative. Pediatric patients diagnosed with inflammatory bowel disease were included. Patients with missing diagnosis or corticosteroid use data were excluded. We performed serial cross-sectional analyses of period prevalence and used multivariate regression models. 27,321 patients were included (65% Crohn disease, 28% ulcerative colitis, 7% indeterminate colitis). Corticosteroids were used in 10,206 (37%). Corticosteroid use decreased from 28% (2007) to 12% (2018). Black patients received corticosteroids more commonly than white patients. This disparity improved as corticosteroid use decreased in both groups. Most corticosteroid use occurred <120 days after diagnosis. Corticosteroid or 5-aminosalicylate use <120 days after diagnosis predicted later corticosteroid use. Anti-tumor necrosis factor-alpha medication use <120 days after diagnosis was associated with a reduction in corticosteroid use. As corticosteroid use decreased, steroid-sparing therapy use increased and height and weight z scores improved, particularly among children with Crohn disease. Despite improvement across the network, variation in corticosteroid usage remains. Corticosteroid use among pediatric patients with inflammatory bowel disease in the ImproveCareNow Network has decreased over time. Racial disparities in corticosteroid use were found, but gradually improved.

A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn’s disease patients in Finland

Background Real-world evidence to support optimal ustekinumab dosing for refractory Crohn’s disease (CD) patients remains limited. Data from a retrospective nationwide chart review study was utilized to explore ustekinumab dosing dynamics and optimization, identify possible clinical predictors of dose intensification, and to evaluate ustekinumab trough concentrations (TCs) and concomitant medication use in Finland. Methods Information gathered from17 Finnish hospitals included clinical chart data from 155 adult CD patients who received intravenous ustekinumab induction during 2017–2018. Data on ustekinumab dosing and TCs, concomitant corticosteroid and immunosuppressant use, and antiustekinumab antibodies were analyzed in a two-year follow-up, subject to availability. Results Among 140 patients onustekinumab maintenance therapy, dose optimization was required in 55(39%) of the patients, and 41/47 dose-intensified patients (87%) persisted on ustekinumab. At baseline, dose-intensified patient group had significantly higher C-reactive protein (CRP) levels, and at week 16, significantly lower ustekinumab TCs than in patients without dose intensification. Irrespective of dose optimization, a statistically significant reduction in the use of corticosteroids was observed at both 16 weeks and one year, coupled with an increased proportion of patients on ustekinumab monotherapy. Antiustekinumab antibodies were undetectable in all 28 samples from 25 patients collected throughout the study period. Conclusions Nearly a third of all CD patients on ustekinumab maintenance therapy, with a history of treatment-refractory and long-standing disease, required dose intensification. These patients persisted on ustekinumab and had significant reduction of corticosteroid use. Increased baseline CRP was identified as the sole indicator of dose intensification. Trial registration EUPAS30920

Efectividad de mepolizumab y benralizumab en una cohorte de pacientes con asma grave eosinofílico en vida real

IntroductionMepolizumab is a monoclonal antibody that inhibits circulating interleukin 5 (IL-5). Benralizumab binds to the alpha subunit of the IL-5 receptor, inducing the direct elimination of eosinophils and basophils. The aim of this study was to evaluate their effectiveness in our routine clinical practice. MethodsA retrospective observational study of a cohort of patients with severe eosinophilic asthma treated with mepolizumab and benralizumab for at least 6 months, and followed up in the asthma unit. ResultsWe analyzed 25 patients who received mepolizumab and 13 who received benralizumab, 73.7% of whom were followed up for 12 months (10 months for benralizumab and 18 for mepolizumab). After biological treatment, there was a 71% reduction in the number of admissions (p=.0027) and a 66% reduction (p=.0013) in emergency visits. A reduction in corticosteroid use was recorded: 31 cycles of corticosteroids compared to 15 after biological treatment, representing a decrease of 52% (p=.0069). Asthma control measured by the Asthma Control Test was 10.8 (SD: 4.73) vs. 20.3 (SD: 4.77), (p=.001) and FEV1% was 70.6% (SD: 21.5) vs. 76.2% (SD: 27.2), (p=.0437). ConclusionsThe effectiveness of anti-IL-5 drugs in real life was confirmed, with improvements in exacerbations, asthma control and lung function.

Efficacy and safety evaluation of avatrombopag in immune thrombocytopenia: analyses of a phase III study and long-term extension

Avatrombopag is an oral thrombopoietin receptor agonist approved for chronic immune thrombocytopenia (ITP). This is a post hoc analysis of the pivotal phase III study (NCT01438840) evaluating additional endpoints not previously described. Thirty-two ITP patients were randomized to avatrombopag and 17 were randomized to placebo during a 26-week core study period (with 21 study visits), followed by an open-label extension period, in which all patients received avatrombopag for varying lengths of time. In this analysis, we evaluated previously unreported response rates at the study visit level, durability of response, and reduction in corticosteroid use with avatrombopag treatment. In the core study, more avatrombopag-treated patients achieved either response (Plt ≥50 000/µL) or complete response (Plt ≥100 000/µL) than placebo-treated patients by day 8 (65.6% vs. 0%; P < .0001 for response; 37.5% vs. 0%; P < .0001 for complete response), day 28 (84.4% vs. 0%; P < .0001 for response; 71.9% vs. 0%; P < .0001 for complete response), and month 6 (87.5% vs. 5.9%; P < .0001 for response; 81.3% vs. 5.9%; P < .0001 for complete response). Durable responders from the core study achieved response and complete response at 96.1% and 60.1% of extension phase visits, respectively. Durable clinically relevant response (Plt ≥30 000/µL for 6 of the final 8 weeks of the core study) occurred in 64.0% of avatrombopag-treated patients versus 0% of placebo-treated patients. More than half (57.1%) of patients on chronic corticosteroids reduced or discontinued corticosteroids. In conclusion, avatrombopag enabled most patients with ITP to achieve clinically meaningful and durable platelet count improvements.

Reduction of corticosteroid use in outpatient treatment of exacerbated COPD\xa0- Study protocol for a randomized, double-blind, non-inferiority study, (The RECUT-trial)

BackgroundChronic obstructive pulmonary disease (COPD) is a major public health issue affecting approximately 4% to 7% of the Swiss population. According to current inpatient guidelines, systemic corticosteroids are important in the treatment of acute COPD exacerbations and should be given for 5 to 7 days. Several studies suggest that corticosteroids accelerate the recovery of FEV1 (forced expiratory volume in 1 second), enhance oxygenation, decrease the duration of hospitalization, and improve clinical outcomes. However, the additional therapeutic benefit regarding FEV1 recovery appears to be most apparent in the first 3 to 5 days. No data are available on the optimum duration of corticosteroid treatment in primary-care patients with acute COPD exacerbations. Given that many COPD patients are treated as outpatients, there is an urgent need to improve the evidence base on COPD management in this setting. The aim of this study is to investigate whether a 3-day treatment with orally administered corticosteroids is non-inferior to a 5-day treatment in acute exacerbations of COPD in a primary-care setting.Methods/designThis study is a prospective double-blind randomized controlled trial conducted in a primary-care setting. It is anticipated that 470 patients with acutely exacerbated COPD will be recruited. Participants are randomized to receive systemic corticosteroid treatment of 40 mg prednisone daily for 5 days (conventional arm, n = 235) or for 3 days followed by 2 days of placebo (experimental arm, n = 235). Antibiotic treatment for 7 days is given to all patients with CRP ≥ 50 mg/l, those with a known diagnosis of bronchiectasis, or those presenting with Anthonisen type I exacerbation. Additional treatment after inclusion is left at the discretion of the treating general practitioner. Follow-up visits are performed on days 3 and 7, followed by telephone interviews on days 30, 90, and 180 after inclusion in the study. The primary endpoint is the time to next exacerbation during the 6-month follow-up period.DiscussionThe study is designed to assess whether a 3-day course of corticosteroid treatment is not inferior to the conventional 5-day treatment course in outpatients with exacerbated COPD regarding time to next exacerbation. Depending on the results, this trial may lead to a reduction in the cumulative corticosteroid dose in COPD patients.Trial registrationClinicalTrials.gov, NCT02386735. Registered on 12 March 2015.

US Practice Patterns and Impact of Monitoring for Mucosal Inflammation After Biologic Initiation in Inflammatory Bowel Disease.

We assessed practice patterns for monitoring mucosal inflammation after biologic initiation and the association between monitoring approaches and development of disease-related complications for Crohn's disease (CD) and ulcerative colitis (UC). This study used a Truven Health MarketScan (2007-2016) query for CD and UC patients initiating biologic therapy. Cumulative 24-month disease-related complications (corticosteroids, change of biologic, hospitalization, surgery) in patients undergoing proactive disease monitoring with lower endoscopy, fecal calprotectin, or cross-sectional radiographic enterography (computed tomography enterography or magnetic resonance enterography) within 6 months of biologic initiation vs no early monitoring after biologic initiation were compared. Cox proportional hazard ratios (HRs with 95% confidence intervals [CIs]) adjusted for propensity score were used. Within the first 24 months after biologic initiation, monitoring (proactive or reactive) was performed in 56.4% of CD patients and 67.8% of UC patients, with considerable geographic variability. Early (within 6 months) proactive monitoring was endoscopy-based (87.9%), performed in 11% of CD (n = 2195/19,899) and 12.8% of UC (n = 925/7247) patients. Compared with no early monitoring, early proactive monitoring was associated with a reduction in disease-related complications for CD (adjusted HR [aHR], 0.90; 95% CI, 0.84-0.96) and UC (aHR, 0.87; 95% CI, 0.78-0.97) and predominately driven by a reduction in corticosteroid use (CD: aHR, 0.83; 95% CI, 0.77-0.90; UC: aHR, 0.77; 95% CI, 0.69-0.87). Results were consistent across multiple sensitivity analyses. Early proactive monitoring of mucosal inflammation in CD and UC within 6 months of biologic initiation was associated with reduction in disease-related complications over 24 months, primarily related to reduced steroid utilization. Wide variation exists in practice patterns for monitoring of mucosal inflammation after biologic initiation.

Clinical outcomes in patients with systemic lupus erythematosus treated with belimumab in clinical practice settings: a retrospective analysis of results from the OBSErve study in Switzerland.

To describe patterns of systemic lupus erythematosus (SLE) care and the clinical effectiveness of belimumab plus standard of care therapy in a real-world clinical setting in Switzerland. This multicentre, observational, retrospective cohort study included adults with SLE who initiated belimumab as part of their usual care at least six months before data analysis. The primary outcome was the overall clinical response, assessed by a physician on a Physician&rsquo;s Global Assessment-like scale, to six months&rsquo; treatment with belimumab. Secondary outcomes included improvement in disease activity, SLE manifestations and changes in corticosteroid use. 53 patients (81% female) from three hospitals were included. At index (belimumab initiation), 23 patients (43%) had mild, 23 (43%) had moderate, and 7 (13%) had severe SLE. Overall improvement in disease activity in patients receiving belimumab was: &ge;80% in 6 patients (11%), &ge;50% in 12 (23%), &ge;20% in 31 (58%), &lt;20% in 13 (25%), and no improvement in 9 (17%). Mean Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index score decreased from 8.0 at index to 3.6 at six months post index in the 27 patients assessed. In addition, a &ge;50% improvement in arthritis, fatigue, rash, low complement (C3, C4 or total haemolytic complement activity), and anti-double-stranded deoxyribonucleic acid antibody levels was experienced six months post index by 10 (38%), 3 (16%), 6 (38%), 2 (12%) and 4 (16%) patients who presented the manifestations at index respectively. At index, 41 patients (77%) received oral corticosteroids at a mean dose of 11.6 mg/day, which decreased to 5.9 mg/day at six months post index. Of the 31 patients receiving a high dose of corticosteroids (&ge;7.5 mg/day) at index, 18 required &lt;7.5 mg/day and a further two discontinued corticosteroids at six months post index. This study provides real-world insight into belimumab use in clinical practice in Switzerland. In line with findings from other countries, Swiss patients with SLE who received belimumab demonstrated clinical and serological improvements in SLE and a reduction in corticosteroid use after six months of treatment.

Reduction in Corticosteroid Use Among Patients Receiving Omalizumab in Real World Settings: A Systematic Literature Review of Non-Randomized Studies

Sarah W. Spriet, DO, Taylor A. Banks, MD, Cecilia Mikita, MD, MPH, FAAAAI; Walter Reed National Military Medical Center, Bethesda, MD. RATIONALE: Rabies post-exposure treatment is a medical necessity. Two rabies vaccines are available in the United States; purified chick embryo cell culture vaccine (PCECV, RabAvert ) and gelatin-free human diploid cell vaccine (HDCV, Imovax ). We report a case of PCECV-triggered anaphylaxis. METHODS: After clinical evaluation, patient and a volunteer control underwent skin prick and intradermal testing to the rabies vaccines, vaccine components, and rabies immunoglobulin. Vaccine challenge was then performed. RESULTS: A healthy 15 year old male presented to the Emergency Department after a live bat was found in his home, captured, and found to have rabies.Mucousmembrane exposure could not be ruled out and human rabies immunoglobulin (ImogamRabies – HT ) and PCECVwere administered. Within minutes, he developed dyspnea, stridor and generalized hives. Symptoms resolved within one hour after treatment with antihistamines and IV corticosteroids and he was referred to AllergyImmunology. On day 3 post-exposure, patient and control underwent skin prick testing to undiluted PCECV, egg, gelatin, HDCVand Imogam. Skin prick was positive to PCECV and gelatin. Intradermal testing (IDT) using 0.02 mL of 1:100 dilution to HDCV and Imogam was negative. IDT using 0.02 mL of 1:10 dilution was negative to Imogam, positive to HDCV; however, considered an irritating dose given identical results in control. Patient tolerated a 10/90 challenge to HDCV and completed post-exposure series using this vaccine. CONCLUSIONS: Skin test results and successful challenge to HDCV suggest gelatin allergy. Awareness of the potential for IgE-mediated reactions to rabies vaccine is important. Challenge to HDCV should be considered in select patients.

OP0044 Effects of Atacicept on Disease Activity in Patients with Moderate to Severe Systemic Lupus Erythematosus: APRIL-SLE Randomized Trial

BackgroundAtacicept is a fusion protein that inhibits B-cell stimulating factors BLyS and APRIL. Levels of these factors are elevated in systemic lupus erythematosus (SLE). Atacicept 150 mg (A150) was associated...

Mo1214 Long-Term Safety and Efficacy of Golimumab in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the PURSUIT-SC Maintenance Study Extension

Mo1214 Long-Term Safety and Efficacy of Golimumab in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the PURSUIT-SC Maintenance Study Extension

OP010 AlphaE integrin expression as a predictive biomarker for induction of clinical remission by etrolizumab: Analysis of a phase II trial in moderate-to-severely active ulcerative colitis

OP010 AlphaE integrin expression as a predictive biomarker for induction of clinical remission by etrolizumab: Analysis of a phase II trial in moderate-to-severely active ulcerative colitis

Reductions in Corticosteroid Use in Patients with Ulcerative Colitis or Crohnʼs Disease Treated with Vedolizumab

Purpose: Long-term corticosteroid use in ulcerative colitis (UC) and Crohn's disease (CD) leads to adverse effects/dependence. The effect of vedolizumab (VDZ), an anti-α4β7 integrin antibody, on corticosteroid reduction has been studied in UC and CD patients (pts). Methods: In two phase 3 studies (GEMINI I [UC] and II [CD]), pts received placebo (PB) or VDZ 300 mg intravenously during induction (weeks 0 and 2) and maintenance (weeks 6-52, every 8 or 4 weeks [Q8W/Q4W]). Pts on corticosteroids at week 0 with a clinical response at week 6 began corticosteroid tapering at week 6. Week 52 corticosteroid-free remission rates (prespecified) and associations between week 6 end points and week 52 corticosteroid-free remission (post hoc) were assessed. Results: In the UC trial, VDZ Q8W and Q4W led to significantly greater week 52 corticosteroid-free remission rates and decreased corticosteroid use for up to 180 d than did PB. Of pts in week 6 remission, significantly more in the VDZ Q4W group than the PB group had corticosteroid-free week 52 remission. In pts with week 6 mucosal healing, week 52 corticosteroid-free remission rates were significantly higher with VDZ Q8W and Q4W than PB. In the CD trial, VDZ also led to significantly greater week 52 corticosteroid-free remission rates (Q8W, Q4W) and decreased corticosteroid use for up to 180 d (Q8W) than did PB. In CD pts in week 6 clinical remission, no significant differences from PB in VDZ week 52 corticosteroid-free remission rates were seen. Conclusion: VDZ treatment led to corticosteroid-free remission in UC and CD patients. Future studies are needed to confirm whether 6-week clinical remissions and/or mucosal healing are predictive of 52-week steroid-free remissions. This research was funded by Millennium Pharmaceuticals, Inc., a Takeda Company, Cambridge, MA. Disclosure - B. Sands - Financial support for research from: Takeda Pharmaceuticals, Abbott Immunology, Janssen Biotech, Celgene, Pfizer, UCB, GlaxoSmithKline, Prometheus Laboratories, Lecture fee(s) from: Mechanisms in Medicine, Creative Educational Concepts, Curatio CME, IMEDEX, Consultancy for: Takeda Pharmaceuticals, Abbott Immunology, Amgen, Astellas Pharmaceutical Global Development, Avaxia Biologics, Axcan Pharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Janssen Biotech, Chandler Chicco Agency, Cornerstones, Emmi Solutions, Elan Pharmaceuticals, Merrimack Pharmaceuticals, Pfizer, Prometheus Laboratories, Kyowa Hakko Kirin Pharma Inc, Vertex Pharmaceuticals, Strategic Consultants International, Dyax, GlaxoSmithKline, Puretech Ventures, Novartis, Baxter Healthcare Corporation, Dainippon Sumitomo Pharm Co, Immune Pharmaceuticals Corporation, Teva Pharmaceuticals, Shareholder of: Avaxia Biologics; S. Hanauer - Financial support for research from: Millennium Pharmaceuticals, Consultancy for: Takeda Pharmaceuticals, Millennium Pharmaceuticals; J.-F. Colombel - Financial support for research from: Ferring, MSD, Abbott Laboratories, Lecture fee(s) from: Abbott Laboratories, Centocor, Ferring, Given Imaging, Shire, MSD, UCB Pharmaceuticals, Tillotts, Consultancy for: Takeda Pharmaceuticals, Abbott Laboratories, Amgen, Biogen Idec Inc, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix SL, Chemocentryx Inc, Centocor, Cosmo Technologies, Elan Pharmaceuticals, Genentech, Giuliani, Given Imaging, GlaxoSmithKline, Hospira, Immune Pharmaceuticals, MSD, Neovacs, Ocera Therapeutics, Pfizer, Prometheus, Shire Pharmaceuticals, Synta Pharmaceuticals, Teva Pharmaceuticals, Therakos, UCB Pharmaceuticals, TXCell, Wyeth, Shareholder of: Intestinal Biotech Development, Other: Takeda Pharmaceuticals, Schering-Plough; S. Danese - Lecture fee(s) from: Vifor Pharma, MSD, Consultancy for: Ferring, Takeda Pharmaceuticals, Abbott, MSD, Vifor Pharma, Novo Nordisk, AstraZeneca, UCB, Pfizer; M. Abreu - Consultancy for: Abbott Laboratories, Bristol-Myers Squibb, Hospira, Merck, Pfizer, Sanofi-Aventis, UCB; V. Ahuja - None Declared; T. Ponich - None Declared; I. Hilmi - None Declared; S. Sankoh - Employee: Millennium Pharmaceuticals; M. Smyth - Shareholder of: Takeda Global Research & Development Centre, Employee: Takeda Global Research & Development Centre, B. Abhyankar - Shareholder of: Takeda Global Research & Development Centre, Employee: Takeda Global Research & Development Centre; I. Fox - Shareholder of: Millennium Pharmaceuticals, Employee: Millennium Pharmaceuticals; B. Feagan - Financial support for research from: Takeda Pharmaceuticals, Lecture fee(s) from: Johnson and Johnson, Abbott Laboratories, UCB, Shire, Consultancy for: Takeda Pharmaceuticals, Johnson and Johnson, Centocor, Elan/Biogen, Bristol-Myers Squibb, Celgene, CombinatoRx, UCB Pharma, Napo Pharma, Abbott Laboratories, Procter and Gamble, Berlex, Ore Pharmaceuticals, Cerimon Pharma, Genentech, Tillotts, Unity Pharmaceuticals, Albireo Pharma, Salix Pharma, Novo Nordisk, GSK, Astra Zeneca, Serono, Given Imaging Inc, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Nektar, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GICare Pharma, Sigmoid Pharma. This research was supported by an industry grant from Millennium Pharmaceuticals, Inc, a Takeda Company.Table

Tiotropium for Adults with Inadequately Controlled Persistent Asthma

To review the literature evaluating the efficacy and steroid-sparing effect of tiotropium for inadequately controlled persistent asthma in adults. Information was obtained through a search of MEDLINE/PubMed (1966-October 2012), using the terms asthma and tiotropium. A further review of reference citations was performed to identify other relevant articles. English-language case reports and clinical trials were reviewed. Publications evaluating the efficacy and steroid-sparing effect of tiotropium in adults with inadequately controlled persistent asthma were included in the review. One case report and 5 clinical trials met our criteria. The ultimate goal for asthma management is to maintain disease control by preventing acute exacerbations while avoiding adverse medication effects. Inhaled corticosteroids (ICS) are part of all preferred maintenance regimens for persistent asthma. Unfortunately, persistent asthma remains inadequately controlled in some patients and concerns about serious adverse effects with long-term high-dose ICS treatment exist. Interest in the use of tiotropium to control asthma symptoms and reduce steroid requirements in inadequately controlled persistent asthma is emerging. Results of several trials indicate that tiotropium improves pulmonary function markers and reduces corticosteroid requirements. Moreover, the largest and longest published trial not only showed improvements in pulmonary function tests but also a reduction in corticosteroid use and an increase in the time to first exacerbation. Although tiotropium use in treatment of persistent asthma appears to be promising, more robust clinical trials are needed to assess whether improved pulmonary function tests as well as a decrease in asthma exacerbations and corticosteroid requirements translate into improvements in quality of life. Additionally, the optimal patient population, long-term efficacy, and safety of tiotropium when delivered by various methods need to be determined before it can be recommended over current alternative asthma therapies.

Reduced Steroid Usage in Ulcerative Colitis Patients With Week 8 Response to Adalimumab: Subanalysis of ULTRA 2

Purpose: To investigate corticosteroid (CS)-free remission and reduction in CS use in adult patients (pts) with moderately to severely active ulcerative colitis (UC) failing conventional therapy who responded to induction with the anti-TNF agent adalimumab (ADA) in the 52-week (wk), double-blind (DB), placebo (PBO)-controlled ULTRA 2 trial.1 Methods: Pts were stratified by prior anti-TNF use and randomized 1:1 to receive ADA induction (160/80 mg) or PBO at wks 0/2, then ADA 40 mg every other week or PBO from wk4. Pts using CS at baseline (BL) were included; CS tapering was allowed (not required) from wk8. Response to induction was assessed at wk8 in ADA-treated pts using full Mayo score (FMS; response=Mayo score decrease of ≥3 points and ≥30% from BL and decrease in rectal bleeding score [RBS] ≥1 or absolute RBS ≤1) and partial Mayo score (PMS, Mayo score without endoscopy subscore; response=PMS decrease ≥2 points and ≥30% from BL, and RBS criteria as above). At wk52, the proportion achieving CS-free remission (Mayo score ≤2, no subscore >1) and the proportion free of CS were compared for ADA-treated pts who responded at wk8 (FMS or PMS) vs. PBO-treated pts, overall (Cochran-Mantel-Haenszel) and by prior anti-TNF use (chi-square). Mean percent changes in CS dose from BL to end of DB treatment were compared (ANOVA). Results: Of 150 ADA-treated pts using CS at BL, 90 (60%) responded per FMS, and 90 (60%) responded per PMS at wk8. Compared with all PBO-treated pts using CS at BL (n=140), significantly more ADA wk8 responders (by FMS or PMS) achieved CS-free remission or were CS-free at wk52 (Table). Similar wk52 results were observed for anti-TNF-naïve and -exposed pts. For ADA-treated wk8 responders, mean percent changes in CS dose from BL to end of DB treatment were -64.4% (FMS) and -68.3% (PMS), vs. -17.5% for PBO-treated pts (P<0.003).Table: No Caption available.Conclusion: In pts with moderately to severely active UC who used CS at BL in ULTRA 2, clinically meaningful long-term CS-free remission and CS-sparing efficacy with ADA was seen at wk52 in pts with wk8 response by full or partial Mayo score. ADA treatment resulted in clinically meaningful reductions in CS doses.

Herbal interventions for chronic asthma in adults and children: a systematic review and meta-analysis

To assess the efficacy of herb and plant extracts in the management of asthma. Systematic review and meta-analysis. Multiple database searches identified randomised placebo controlled trials of herbal interventions reporting at least one primary outcome measure. Where possible data were combined for meta-analysis. Primary outcome measures were lung function, exacerbations and reduction in corticosteroid use. Secondary outcome measures were symptoms and symptom scores, use of reliever medications, changes in rates of consultation and adverse effects. Twenty-six studies reporting on 20 herbal preparations were included. Two of six studies reporting change in FEV1 were positive. Little data was available on frequency of exacerbations. For primary outcomes single studies of Boswellia, Mai-Men-Dong-Tang, Pycnogenol, Jia-Wei-Si-Jun-Zi-Tang and Tylophora indica showed potential to improve lung function, and a study of 1.8-Cineol (eucalyptol) showed reduced daily oral steroid dosage. Improvements in symptoms were not strongly supported by objective changes. Most trials were of small sample size, short duration, and poor methodology. Further adequately powered trials are needed to assess these compounds. Such trials should conform to CONSORT guidance, report standardised spirometry, and use validated symptom and severity scores. No recommendations for herbal treatment of asthma can be made from the current evidence.