Oral Beclomethasone Research Articles

Efficacy and safety of oral beclomethasone dipropionate and budesonide MMX versus 5-aminosalicylates or placebo in ulcerative colitis: a systematic review and meta-analysis.

Low bioavailability steroids, including beclomethasone dipropionate (BDP) and budesonide MMX, have been developed to ensure colonic targeting and low systemic activity than systematic corticosteroids in treating patients with ulcerative colitis (UC). This systematic review and meta-analysis evaluated the efficacy and safety of BDP and budesonide MMX® compared with 5-aminosalicylic acid (5-ASAs) or placebo, in patients with mild-to-moderate UC. Systematic review and meta-analysis. We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials from inception to December 2021. We included all available randomized controlled trials (RCTs) comparing oral BDP or budesonide MMX with 5-ASAs or with placebo in induction of remission of mild-to-moderate UC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. We identified two RCTs comparing BDP 5 mg with 5-ASA, one RCTs comparing BDP 10 mg with 5-ASA, two RCTs BDP 5 mg versus placebo, one RCT BDP 10 mg versus placebo, two RCTs budesonide MMX 9 mg versus 5-ASA, and six RCTs budesonide MMX 9 mg versus placebo. In terms of achieving clinical remission or improvement, BDP 5 mg, BDP 10 mg, and budesonide MMX 9 mg were more effective than placebo (OR 2.36, 95% CI 1.37-4.08; OR 2.23, 95% CI 1.02-4.87; and OR 2.03, 95% CI 1.45-2.85, respectively). The drugs were also more effective than placebo in achieving endoscopic remission. Regarding the comparisons with 5-ASA, we found no differences between 5-ASA and BDP 5 mg or BDP 10 mg or budesonide MMX 9 mg in achieving clinical remission or improvement (OR 0.90, 95% CI 0.51-1.57; OR 1.54, 95% CI 0.42-5.64; and OR 1.17, 95% CI 0.82-1.66). However, 5-ASA was more effective than budesonide MMX 9 mg in achieving histological remission (OR 0.33, 95% CI 0.16-0.70). Overall, all the drugs were safe and well tolerated. Low bioavailability steroids were more effective than placebo in achieving clinical remission, clinical and endoscopic remission, and histological remission. No differences were found between 5-ASA and BDP or budesonide MMX. Surely, more RCTs, also comparing BDP and budesonide MMX, are mandatory to confirm or not these results.

Oral beclomethasone dipropionate is an effective treatment for immune checkpoint inhibitor induced colitis

IntroductionSystemic corticosteroids are the mainstay of treatment for immune checkpoint inhibitor induced (CPI) colitis but are associated with complications including life-threatening infection. The topically acting oral corticosteroid beclomethasone dipropionate (BD)...

Oral beclomethasone dipropionate as an add-on therapy and response prediction in Korean patients with ulcerative colitis.

We aimed to investigate the oral beclomethasone dipropionate's (BDP) efficacy as an add-on therapy and to clarify the predictive factor for response to oral BDP in Korean ulcerative colitis (UC) patients. Patients with a stable concomitant drug regimen with exposure to oral BDP (5 mg/day) within 30 days before BDP initiation were included. Partial Mayo score (pMS) was used to evaluate response to oral BDP. Clinical remission (CREM) was defined as a post-treatment pMS ≤ 1 point. Clinical response (CRES) was defined as an at least 2-point decrease in post-treatment pMS and an at least 30% decrease from baseline pMS. Patients without CREM or CRES were considered nonresponders (NRs). Of all, 37 showed CREM, 19 showed CRES, and 44 were NRs. The CREM group included more patients with mild disease activity (75.7% vs. 43.2%, p = 0.011) than NRs. In contrast to NRs, CREM and CRES patients showed significant improvement of post-treatment erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (ESR with p = 0.001, CRP with p = 0.004, respectively). Moreover, the initial rectal bleeding subscore (RBS) was significantly different between CREM and CRES, or NR (both with p < 0.001). In multivariate analyses, initial stool frequency subscore (SFS) of 0 and RBS of 0 were predictive factors for CREM (odds ratio [OR], 15.359; 95% confidence interval [CI], 1.085 to 217.499; p = 0.043 for SFS, and OR, 11.434; 95% CI, 1.682 to 77.710; p = 0.013 for RBS). Oral BDP is an efficacious add-on therapy in Korean UC patients. Patients with initial SFS or RBS of 0 may be particularly good candidates for oral BDP.

P448 Oral beclomethasone dipropionate as an add-on therapy and response prediction in Korean patients with ulcerative colitis

Abstract Background We aimed to investigate the efficacy of oral beclomethasone dipropionate (BDP) as an add-on therapy to concomitant drugs and to clarify the predictive factors for response to oral BDP in Korean patients with ulcerative colitis (UC). Methods Patients with a stable concomitant drug regimen with exposure to oral BDP (5 mg/day) within 30 days before initiation were included. The partial Mayo score (pMS) was used to evaluate response to oral BDP. Clinical remission (CREM) was defined as a posttreatment pMS ≤1 point. Clinical response (CRES) was defined as an at least 2-points decrease in the posttreatment pMS and an at least 30% decrease from the baseline pMS. Patients without CREM or CRES were considered nonresponders (NRs). Results Of total 100 patients, 37 showed CREM, 19 showed CRES, and 44 were NRs (Table 1). The CREM group included more patients with mild disease activity (75.7% vs. 43.2%, P=0.011) than the NR group. In contrast to NR group, responders including CREM and CRES showed significant improvement of posttreatment ESR and CRP (ESR with P=0.001, CRP with P=0.004, respectively). Moreover, initial rectal bleeding subscore (RBS) was significantly different between CREM and CRES, or NR (both with P<0.001). In multivariate logistic regression analysis, initially mild disease activity was the only predictive factor for CREM (odds ratio, 3.580; 95% confidence interval, 1.342–9.548) (Table 2). Conclusion Oral BDP is efficacious as an add-on therapy in Korean UC patients. In case of acute aggravation, patients with mild disease activity, especially low RBS, may be good candidates for oral BDP.

Ruxolitinib for Treating Steroid-Refractory Acute Graft-Versus-Host Disease in an Infant with Malignant Osteopetrosis Who Received Double-Unit Umbilical Cord Blood Transplantation

A 3-month-old male infant was transferred to our hospital due to bicytopenia. His bone marrow biopsy showed irregular bony trabeculae with cartilaginous core, which was consistent with osteopetrosis. In the genetic test, c.242del (p.Pro81Argfs*85) in TCIRG1 was found to be homozygotic, thus he was diagnosed with malignant infantile osteopetrosis. At 6 months of age, he received double-unit umbilical cord blood transplantation (UCBT) with the conditioning regimen including busulfan, cyclophosphamide, and rabbit anti-thymocyte globulin. Initially, single UCB was infused to the patient, but the post infusion viability of the UCB was unexpectedly low. Thus, another UCB was additionally infused. Cyclosporine and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. Neutrophils and platelets were engrafted on day +13 and +33, respectively. With engraftment, he showed overall grade 4 acute GVHD involving the skin and gut, which was refractory to corticosteroids. Despite treating with low-dose weekly methotrexate (10 mg/m2) and oral beclomethasone, his symptoms persisted. After treating with ruxolitinib 2.5 mg/day for 2 weeks, and 5 mg/day thereafter, his diarrhea stopped in 2 weeks and his skin symptoms gradually improved over 3 months. The short tandem repeats showed 100% donor chimerism at 1 and 3 months after UCBT. Currently, 4 months after UCBT, he is 10 months old. The oral prednisolone has been tapered to 0.6 mg/kg/day, and the dose of ruxolitinib was decreased to 2.5 mg/day without recurrence of GVHD. We plan to taper off the immunosuppressive agents if his GVHD symptoms do not recur. Keywords: Child, Cord blood stem cell transplantation, Graft vs host disease, Infant, Osteopetrosis

Outcome of gastrointestinal graft-versus-host disease according to the treatment response

The optimal treatment strategy for gastrointestinal graft-versus-host disease (GI-GVHD) after allogeneic hematopoietic cell transplantation remains to be established. We retrospectively analyzed 68 cases of GI-GVHD at our institution between 2007 and 2017. The survival outcomes were significantly inferior in patients who did not respond to the first-line treatment (1-year overall survival 27.3 vs 69.2%, P = 0.0017; non-relapse mortality 50.0 vs 18.6%, P = 0.026). After subsequent treatments, 18 patients were refractory to all steroid-based treatments such as steroid pulse therapy and oral beclomethasone dipropionate (BDP). However, these steroid-refractory cases showed a gradual increase in the response rate after the initial diagnosis of steroid refractoriness. This result may be explained by the problem of evaluating the response based solely on the volume of diarrhea, i.e., severe mucosal damage due to refractory GI-GVHD may require a long recovery and sometimes be complicated with other diseases. In conclusion, patients with GI-GVHD who failed to respond to the first-line treatment had inferior survival. However, later improvement may be observed without additional immunosuppressant other than steroid among patients who initially do not respond to steroid therapy. It is important to repeat colonoscopy in patients with refractory GI-GVHD to monitor the activity of GVHD.

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).

A green route to beclomethasone dipropionate nanoparticles via solvent anti-solvent precipitation by using subcritical water as the solvent

Oral beclomethasone dipropionate (BDP) has been extensively studied in the management of ulcerative colitis in clinical practice in recently years. However, the effective bioavailability and absorption of BDP are limited by its poor water solubility when administered orally. Herein, we report a green process for the synthesis of BDP nanoparticles via solvent anti-solvent precipitation, in which the subcritical water (SBCW) and cold water were used as the solvent and anti-solvent respectively. Polyethylene glycol (PEG), a non-ionic, hydrophilic polymer was introduced as stabilizers in the SBCW process to obtain sub-50nm BDP nanoparticles with improved dissolution rate. Scanning electronic microscopy (SEM), Fourier transform infrared (FTIR) spectrophotometry, powder X-ray diffraction (XRD) and dissolution tests were performed to investigate the corresponding particle morphology, structure and dissolution rate properties of the BDP nanoparticles. The obtained BDP nanoparticles are <50nm in diameters with uniform distribution, exhibiting similar chemical structures, lower crystallinity and much higher dissolution rate than the raw BDP drug. These results show that as-synthesized BDP nanoparticles are promising for oral administration of BDP towards the management of ulcerative colitis.

Efficacy and Safety of Oral Beclomethasone Dipropionate in Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Background and AimWe performed a systematic review and meta-analysis of all the available evidence comparing efficacy and safety of oral prolonged released beclomethasone dipropionate (BDP) to active oral controls in patients with mild-to-moderate ulcerative colitis (UC). A subgroup-analysis compared the effectiveness of BDP and 5-ASA.MethodsLiterature research was performed in different databases, as well as manual search to identify abstracts from international meetings with data not included in extensive publications. Experts in the field and companies involved in BDP development and manufacture were contacted to identify unpublished studies used for registration purposes. Dichotomous data were pooled to obtain odds ratio meta-analysis.ResultsFive randomized controlled trials that compared oral BDP 5mg/day vs. all oral active controls in treating UC were identified as eligible. Efficacy and safety have been addressed after 4-week treatment period. One study evaluated efficacy and safety of BDP vs. prednisone and 4 of BDP vs. 5-ASA. Treatment with oral BDP 5 mg/day induces a significant better clinical response compared to oral 5-ASA (OR 1.86, 95% CI = 1.23–2.82, P = 0.003). The effect is detectable even when the comparison to prednisone is added (OR 1.41, 95% CI = 1.03–1.93, P = 0.03). Data on remission indicate that the potential clinical efficacy of BDP may be better than 5-ASA (OR 1.55, 95% CI = 1.00–2.40, P = 0.05). This difference is lost when the comparison with prednisone is added (OR 1.30, 95% CI = 0.76–2.23, P = 0.34). The safety analysis showed no differences between BDP and 5-ASA (OR 0.55, 95% CI = 0.24–1.27, P = 0.16). The lack of difference is maintained even when the study with prednisone is added (OR 0.67, 95% CI = 0.44–1.01, P = 0.06). However, the trend of difference is clear and indicates a more favourable safety profile of BDP compared to 5-ASA and PD.ConclusionsOral prolonged release BDP showed a superior efficacy vs. oral 5-ASA in inducing clinical improvement of mild-to-moderate UC with a similar safety profile.

Clinical Efficacy of Beclomethasone Dipropionate in Korean Patients with Ulcerative Colitis.

PurposeOur aim was to evaluate the efficacy and safety of oral beclomethasone dipropionate (BDP) in Korean patients with ulcerative colitis (UC).Materials and MethodsThe medical records of patients with active UC who were treated with BDP were retrospectively reviewed. Partial Mayo Clinic score (pMS) was calculated to determine disease activity. After 4 weeks of therapy, clinical remission, clinical response, and response failure rates were evaluated. Clinical remission was defined as a post-treatment pMS of 0 or 1, clinical response as a decrease of two of three points in pMS and >30% from baseline, and response failure as a lack of clinical response. Also, we considered that clinical remission was included in clinical response.ResultsBetween July 2013 and April 2015, 95 patients with UC received BDP therapy at our institution (median age, 44 years; range, 12–81 years). After 4 weeks of therapy, clinical remission and clinical response rates were 50.5% and 73.7%, respectively. Mean change of pMS before and after BDP therapy was 2.4. There was no significant side effect reported. In multivariate analysis, disease activity was the only factor associated with a favorable response. Clinical remission rate was significantly higher in the mild disease activity group (66.7%) than that in the moderate or severe disease activity group (41.9%) (p=0.024).ConclusionBDP is efficacious in inducing a clinical response or remission in Korean patients with UC. Patients with mild UC were more likely to be in remission than those with moderate or severe UC after receiving BDP for 4 weeks. BDP exhibited a good safety profile.

移植片対白血病効果を保ちつつベクロメタゾン腸溶性製剤で腸管移植片対宿主病抑制を得た急性期慢性骨髄性白血病

移植片対白血病効果を保ちつつベクロメタゾン腸溶性製剤で腸管移植片対宿主病抑制を得た急性期慢性骨髄性白血病

PS-071 Telaprevir-induced Stevens-Johnson Syndrome. A case report

BackgroundThe introduction of triple treatment for the treatment of hepatitis C virus (HCV) has achieved cure rates of 75% in genotype 1 treatment-naïve patients and about 50% in those who...

Oral beclomethasone dipropionate in chronic refractory pouchitis

BackgroundPouchitis is the major long-term complication after ileal-pouch anal-anastomosis for ulcerative colitis. Ten to 15% of patients develop chronic pouchitis, either treatment responsive or treatment refractory. AimTo evaluate the efficacy of oral beclomethasone dipropionate in inducing remission and improving quality of life in patients with chronic refractory pouchitis. MethodsTen consecutive patients with active pouchitis, not responding to 1-month antibiotic treatment, were treated with beclomethasone dipropionate 10mg⁄day for 8weeks. Clinical, endoscopic and histological evaluations were undertaken before and after treatment, according to the Pouchitis Disease Activity Index (PDAI). Remission was defined as a combination of PDAI clinical score of ≤2, endoscopic score of ≤1 and a total PDAI score of ≤4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire (IBDQ). ResultsEight of 10 patients (80%) achieved remission. The median total PDAI scores before and after therapy were, respectively, 12 (range 8–14) and 3 (range 2–9) (P<0.001). The median IBDQ score also significantly improved from 120 (range 77–175) to 175 (range 85–220) (p<0.001). ConclusionEight-week treatment with oral beclomethasone dipropionate appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment.

消化管GVHD（graft-versus-host disease）に対する経口ベクロメタゾン製剤の有用性の検討

消化管GVHD（graft-versus-host disease）に対する経口ベクロメタゾン製剤の有用性の検討

Efficacy and Safety Of Lower-Dose Glucocorticoids For Initial Treatment Of Acute Graft-Versus-Host Disease: A Randomized Controlled Trial

BackgroundAlthough prospective randomized studies have identified no demonstrable benefit for treatment of acute GVHD with methylprednisolone at doses >2 mg/kg/day, the minimum effective dose of methylprednisolone has not been defined. In a previous retrospective comparison of patients who initiated acute GVHD-treatment with prednisone-equivalent doses of 1 mg/kg/day or 2 mg/kg/day, the cumulative prednisone doses at day-42 of treatment were 31 mg/kg and 58 mg/kg, respectively (Mielcarek et al., Blood 2009). We therefore conducted a prospective phase III study to test the hypothesis that initial treatment of acute GVHD with “lower-dose” prednisone (prednisone-equivalent doses ≤1 mg/kg/day) is effective and safe. MethodsPatients with newly diagnosed acute GVHD (≥ Grade IIa) after allogeneic hematopoietic cell transplantation between 2009 and 2013 were eligible for the study. Patients were stratified according to severity of GVHD at symptom-onset. Patients with Grade IIa manifestations (upper gastrointestinal symptoms of anorexia, nausea, vomiting attributed to acute GVHD, with stool volumes <1 L/day, rash involving <50% of the body surface, and no hepatic dysfunction) were randomized to initiate GVHD-therapy with a prednisone-equivalent dose of either 1 or 0.5 mg/kg/day. Those with Grade IIb-IV manifestations (rash involving ≥50% of the body surface, stool volumes ≥1 L/day or hepatic involvement with total serum bilirubin >2 mg/dL) were randomized to start treatment with a prednisone-equivalent dose of either 2 or 1 mg/kg/day. Medications administered for GVHD-prophylaxis were continued as tolerated, and oral beclomethasone dipropionate and budesonide were typically used in combination with systemic glucocorticoids in patients with gastrointestinal GVHD. The rate of prednisone withdrawal was not prescribed by the protocol. The primary endpoint of the study was a ≥33% reduction of cumulative prednisone exposure by day-42 after initiation of treatment among patients given lower-dose prednisone compared to those given higher-dose prednisone. Measures of prednisone toxicity (infections, hyperglycemia) and possible harm (progression to Grade III/IV GVHD, secondary therapy for refractory GVHD, non-relapse mortality, recurrent malignancy) were secondary endpoints. ResultsOne-hundred and fifty patients were enrolled on the study (Grade IIa manifestations, n=92; Grade IIb-IV manifestations, n=58). For patients with Grade IIa GVHD treated initially with either 1 or 0.5 mg/kg, the cumulative prednisone doses at day-42 of treatment were 27.1 vs 22.2 mg/kg, respectively (18% reduction; p=0.08). For patients with Grade IIb-IV GVHD treated initially with either 2 or 1 mg/kg, cumulative prednisone doses at day-42 were 41.3 vs 38.4 mg/kg, respectively (7% reduction; p=0.4) (Figure 1). With a median follow-up of 27 (1-48) months, there were no significant differences in the risks of non-relapse mortality, recurrent malignancy and overall survival among patients started on higher-dose compared to those started on lower-dose initial therapy (15% vs 15%; 17% vs 11%; 76% vs 77%, respectively). Patients with Grade IIb-IV GVHD who started treatment with lower-dose prednisone were more likely to require secondary systemic immunosuppressive therapy than those who started treatment with higher-dose prednisone (41% vs 7%, p=0.001), and a trend suggested an increase in the risk of progression to Grade III-IV acute GVHD (19% vs 7%, p=0.2). The risks of infection and measures of glycemic control were not affected by initially assigned prednisone dose. [Display omitted] ConclusionsThe primary endpoint of the study (≥33% reduction of cumulative prednisone exposure by day-42) was not reached due to the evolving practice of rapid prednisone withdrawal in responding patients treated with the higher dose. For patients presenting with Grade IIa GVHD manifestations, initiating treatment with lower-dose prednisone (0.5 mg/kg/day) was safe and effective. For patients presenting with Grade IIb-IV manifestations, however, initial treatment with lower-dose prednisone (1 mg/kg/day) was associated with an increased likelihood of requiring secondary immunosuppressive therapy without adversely affecting survival. Disclosures:No relevant conflicts of interest to declare.

Oral high dose Beclomethasone dipropionate for treatment of active ulcerative colitis

Oral corticosteroids (CS) have been widely used for treatment of ulcerative colitis (UC) at the price of systemic side effects. Role of topically active oral beclomethasone dipropionate (BDP) in clinical practice is still unclear. The aim of this paper is to investigate efficacy and tolerability of a high dose BDP regimen in mild to moderately active UC. Twenty-five patients (9 males, aged 25-40 years) with mild to moderately active UC, unresponsive to oral and topical 5-ASA (4.8 gr daily) and BDP (5 mg daily), were enrolled. All patients continued 5-ASA plus high dose oral BDP (15 mg od for 4 weeks and than tapered). Clinical, endoscopic, histological and laboratory parameters were monitored. Mean disease activity index (DAI) score at study entry was 8.82±4. Response to treatment was observed in all patients after 2 weeks. Remission was observed in all patients within 4-6 weeks from entering the study (mean DAI score: 2.34±0.5) and maintained throughout 6-month follow-up. No major adverse events were documented. Quality of life global evaluation score improved. This study provides the first evidence of efficacy and safety of high dose oral BDP-scheme in UC demonstrating excellent tolerability and favourable acceptability profile. This new BDPscheme might be a valid alternative to conventional oral CS when standard dose BDP is not effective. Future studies are needed to explore further clinical indications.

Oral Beclomethasone Dipropionate: A Critical Review of its Use in the Management of Ulcerative Colitis and Crohn’s Disease

Crohn's disease and ulcerative colitis are inflammatory bowel diseases characterised by a chronic relapsing course. Corticosteroids represent the mainstay of medical treatment of inflammatory bowel disease for the induction of remission. Despite the high efficacy of systemic steroids, their use is limited by the high incidence of potentially serious adverse effects. The topically acting steroids are synthetic compounds characterised by high anti-inflammatory activity and low systemic effects by virtue of efficient first-pass hepatic inactivation. Budesonide and Beclomethasone Dipropionate are the two most studied topically acting steroids in inflammatory bowel disease. Oral Budesonide has been extensively studied in the treatment of mild to moderate ileo-caecal Crohn's disease but few data are available concerning oral Beclomethasone Dipropionate. This review focuses on the available evidence of efficacy and safety of oral Beclomethasone Dipropionate in the management of ulcerative colitis and Crohn's disease and a possible role of this steroid in clinical practice is suggested.

P380 Oral beclomethasone dipropionate in the treatment of chronic refractory pouchitis

P380 Oral beclomethasone dipropionate in the treatment of chronic refractory pouchitis

Evaluation of Oral Beclomethasone Dipropionate for Prevention of Acute Graft-versus-Host Disease

Results from two randomized trials have shown that oral beclomethasone dipropionate (BDP) is effective for treatment of acute gastrointestinal graft-versus-host disease. Here, we report results of a double-blind, randomized placebo-controlled phase II study designed to test the hypothesis that acute graft-versus-host disease could be prevented by administration of oral BDP, beginning before hematopoietic cell transplantation and continuing until day 75 after hematopoietic cell transplantation after myeloablative conditioning. Study drug (BDP or placebo) was administered as 1-mg immediate-release formulation plus 1-mg delayed-release formulation orally four times daily. According to the primary endpoint, systemic glucocorticoid treatment for graft-versus-host disease was given to 60 of the 92 participants (65%) in the BDP arm, versus 31 of 46 participants (67%) in the placebo arm. The secondary efficacy endpoints showed no statistically significant differences between the two arms. The proportion of participants who took at least 90% of the prescribed study drug during the first 4 weeks after hematopoietic cell transplantation was 54% overall. Lower severity of mucositis strongly correlated with higher adherence to the schedule of study drug administration. Inconsistent adherence related to mucositis during recovery after myeloablative conditioning may have obscured a beneficial therapeutic effect in the current study.

Adverse effects during specific oral tolerance induction: in home phase

Specific oral tolerance induction (SOTI) is a promising approach for severe food allergies. There are little data in the literature regarding the home-phase of SOTI, not only with regard to type and frequency of adverse reactions but also regarding the most suitable treatment and protocol. To define the incidence and severity of adverse reactions, possible risk factors, and the safety and effectiveness of the home-phase of an original SOTI protocol in a large group of children with severe cow's milk (CM) allergy, after the hospital "rush" phase. The study was conducted by recording in-home phase adverse events, success and failure as reported by parents, and calling families. Adverse reactions were treated following the International Guidelines, arbitrarily modified by introducing nebulised epinephrine for respiratory reactions, oral beclomethasone for acute gastric pain and oral cromolyn for recurrent gastric pain. Out of 140 patients, 132 were contacted; eight were inaccessible (follow-up 2-84 months). The number of adverse reactions was 1 in every 100 doses. The reactions were treated with nebulised epinephrine (221 reactions), IM epinephrine (6 reactions), and other drugs. Patients with high specific IgE levels (greater than 100 kU(A)/L) and lower CM dose (less than 5 ml) at the end of in-hospital phase showed a higher risk both for number of reactions and use of nebulised epinephrine. The home phase of SOTI was characterised by a significant number of adverse reactions, mostly managed with an acceptable rate of side effects. Nebulised epinephrine played a pivotal role in respiratory reactions.