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Treatment with budesonide oral suspension (BOS) was generally well tolerated and maintained a histologic response in some patients with eosinophilic esophagitis (EoE), according to the results of the 24-week, open-label extension phase of a multicenter, randomized, placebo-controlled, industry-sponsored trial.
Rates of histologic response (up to 6 eosinophils per high-power field) were “modest” – 23% among patients who stayed on BOS throughout the study and 48.5% among patients who initiated BOS after 12 weeks on placebo, reported Evan S. Dellon, MD, MPH, of the University of North Carolina in Chapel Hill and his associates. However, these rates “need to be viewed in the context of a highly symptomatic and histologically severe population with eosinophilic esophagitis,” they contended. A total of 11% of budesonide initiators developed esophageal candidiasis, they reported in Clinical Gastroenterology and Hepatology.
Budesonide oral suspension is a mucoadherent formulation of topical corticosteroid that has recently been developed to treat EoE. Previously, during the randomized, double-blind component of this phase 2 trial, 93 patients aged 11-40 years with active EoE and dysphagia received either BOS (2 mg) or placebo twice daily (Gastroenterology. 2017 Mar;157[4]:776-86). After 12 weeks, rates of histologic response were 39% for BOS versus 3% for placebo, and BOS significantly improved patients’ mean peak eosinophil count and scores on the Dysphagia Symptom Questionnaire, compared with baseline and compared with the response in the placebo group. During the open-label extension phase, 45 BOS continuers and 37 BOS initiators received 2 mg once daily for 12 weeks and then had the option to increase the BOS dose to 1.5-2.0 mg twice daily.
The rate of drug-related adverse events was 19% among BOS initiators and 4% among BOS continuers. One patient in each group developed oral candidiasis, while four BOS initiators (11%) developed esophageal candidiasis. Three BOS continuers had subnormal morning cortisol levels; while these were subclinical cases, they merit attention since long-term corticosteroids for EoE have been linked with possible hypothalamic–pituitary–adrenal axis suppression, the researchers noted.
In addition, while BOS initiators tended to maintain their endoscopic response, only 42% of those with an initial histologic response maintained a histologic response after 36 weeks of treatment or when leaving the study. Post hoc analyses confirmed that prolonged BOS treatment does not increase the chances of histologic or endoscopic response. Prior studies have suggested that EoE can become steroid-refractory over time and that certain molecular and histologic markers might predict resistance, the investigators noted.
Meritage Pharma (now part of Shire) was involved in the study design and conduct, data collection and management, and manuscript review. Dr. Dellon disclosed research funding from Meritage and Shire and a consulting relationship with Shire, along with ties to several other pharmaceutical companies. All six coinvestigators also disclosed ties to Meritage, Shire, or both, and two are Shire employees and stockholders.
*This story was updated on Feb. 7, 2019.
SOURCE: Dellon ES et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.051.
Guidelines regarding the management of eosinophilic esophagitis (EoE) with topical steroids are still unclear with regard to dosing and duration. Here, Dellon et al. present evidence that long-term budesonide oral suspension (BOS) therapy is safe and efficacious. Both the BOS and placebo cohorts of the initial, 12-week trial demonstrated clinical and histologic improvement on BOS over this 24-week period, with few adverse events. Maintenance of histologic response was only seen in 42% in initial BOS responders, suggesting steroid tolerance or resistance may develop. Another important observation was that peak eosinphil count decreased steroid dosing.
Finally, these data support the notion that initial responders are unlikely to gain response with continued therapy and may be better served with early transition to alternatives. Further research is needed to clarify these issues and which patients may be predisposed to nonresponse or loss of response.
Reena V. Chokshi, MD , is assistant professor of medicine in the department of gastroenterology at Baylor College of Medicine, Houston.
Guidelines regarding the management of eosinophilic esophagitis (EoE) with topical steroids are still unclear with regard to dosing and duration. Here, Dellon et al. present evidence that long-term budesonide oral suspension (BOS) therapy is safe and efficacious. Both the BOS and placebo cohorts of the initial, 12-week trial demonstrated clinical and histologic improvement on BOS over this 24-week period, with few adverse events. Maintenance of histologic response was only seen in 42% in initial BOS responders, suggesting steroid tolerance or resistance may develop. Another important observation was that peak eosinphil count decreased steroid dosing.
Finally, these data support the notion that initial responders are unlikely to gain response with continued therapy and may be better served with early transition to alternatives. Further research is needed to clarify these issues and which patients may be predisposed to nonresponse or loss of response.
Reena V. Chokshi, MD , is assistant professor of medicine in the department of gastroenterology at Baylor College of Medicine, Houston.
Guidelines regarding the management of eosinophilic esophagitis (EoE) with topical steroids are still unclear with regard to dosing and duration. Here, Dellon et al. present evidence that long-term budesonide oral suspension (BOS) therapy is safe and efficacious. Both the BOS and placebo cohorts of the initial, 12-week trial demonstrated clinical and histologic improvement on BOS over this 24-week period, with few adverse events. Maintenance of histologic response was only seen in 42% in initial BOS responders, suggesting steroid tolerance or resistance may develop. Another important observation was that peak eosinphil count decreased steroid dosing.
Finally, these data support the notion that initial responders are unlikely to gain response with continued therapy and may be better served with early transition to alternatives. Further research is needed to clarify these issues and which patients may be predisposed to nonresponse or loss of response.
Reena V. Chokshi, MD , is assistant professor of medicine in the department of gastroenterology at Baylor College of Medicine, Houston.
Treatment with budesonide oral suspension (BOS) was generally well tolerated and maintained a histologic response in some patients with eosinophilic esophagitis (EoE), according to the results of the 24-week, open-label extension phase of a multicenter, randomized, placebo-controlled, industry-sponsored trial.
Rates of histologic response (up to 6 eosinophils per high-power field) were “modest” – 23% among patients who stayed on BOS throughout the study and 48.5% among patients who initiated BOS after 12 weeks on placebo, reported Evan S. Dellon, MD, MPH, of the University of North Carolina in Chapel Hill and his associates. However, these rates “need to be viewed in the context of a highly symptomatic and histologically severe population with eosinophilic esophagitis,” they contended. A total of 11% of budesonide initiators developed esophageal candidiasis, they reported in Clinical Gastroenterology and Hepatology.
Budesonide oral suspension is a mucoadherent formulation of topical corticosteroid that has recently been developed to treat EoE. Previously, during the randomized, double-blind component of this phase 2 trial, 93 patients aged 11-40 years with active EoE and dysphagia received either BOS (2 mg) or placebo twice daily (Gastroenterology. 2017 Mar;157[4]:776-86). After 12 weeks, rates of histologic response were 39% for BOS versus 3% for placebo, and BOS significantly improved patients’ mean peak eosinophil count and scores on the Dysphagia Symptom Questionnaire, compared with baseline and compared with the response in the placebo group. During the open-label extension phase, 45 BOS continuers and 37 BOS initiators received 2 mg once daily for 12 weeks and then had the option to increase the BOS dose to 1.5-2.0 mg twice daily.
The rate of drug-related adverse events was 19% among BOS initiators and 4% among BOS continuers. One patient in each group developed oral candidiasis, while four BOS initiators (11%) developed esophageal candidiasis. Three BOS continuers had subnormal morning cortisol levels; while these were subclinical cases, they merit attention since long-term corticosteroids for EoE have been linked with possible hypothalamic–pituitary–adrenal axis suppression, the researchers noted.
In addition, while BOS initiators tended to maintain their endoscopic response, only 42% of those with an initial histologic response maintained a histologic response after 36 weeks of treatment or when leaving the study. Post hoc analyses confirmed that prolonged BOS treatment does not increase the chances of histologic or endoscopic response. Prior studies have suggested that EoE can become steroid-refractory over time and that certain molecular and histologic markers might predict resistance, the investigators noted.
Meritage Pharma (now part of Shire) was involved in the study design and conduct, data collection and management, and manuscript review. Dr. Dellon disclosed research funding from Meritage and Shire and a consulting relationship with Shire, along with ties to several other pharmaceutical companies. All six coinvestigators also disclosed ties to Meritage, Shire, or both, and two are Shire employees and stockholders.
*This story was updated on Feb. 7, 2019.
SOURCE: Dellon ES et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.051.
Treatment with budesonide oral suspension (BOS) was generally well tolerated and maintained a histologic response in some patients with eosinophilic esophagitis (EoE), according to the results of the 24-week, open-label extension phase of a multicenter, randomized, placebo-controlled, industry-sponsored trial.
Rates of histologic response (up to 6 eosinophils per high-power field) were “modest” – 23% among patients who stayed on BOS throughout the study and 48.5% among patients who initiated BOS after 12 weeks on placebo, reported Evan S. Dellon, MD, MPH, of the University of North Carolina in Chapel Hill and his associates. However, these rates “need to be viewed in the context of a highly symptomatic and histologically severe population with eosinophilic esophagitis,” they contended. A total of 11% of budesonide initiators developed esophageal candidiasis, they reported in Clinical Gastroenterology and Hepatology.
Budesonide oral suspension is a mucoadherent formulation of topical corticosteroid that has recently been developed to treat EoE. Previously, during the randomized, double-blind component of this phase 2 trial, 93 patients aged 11-40 years with active EoE and dysphagia received either BOS (2 mg) or placebo twice daily (Gastroenterology. 2017 Mar;157[4]:776-86). After 12 weeks, rates of histologic response were 39% for BOS versus 3% for placebo, and BOS significantly improved patients’ mean peak eosinophil count and scores on the Dysphagia Symptom Questionnaire, compared with baseline and compared with the response in the placebo group. During the open-label extension phase, 45 BOS continuers and 37 BOS initiators received 2 mg once daily for 12 weeks and then had the option to increase the BOS dose to 1.5-2.0 mg twice daily.
The rate of drug-related adverse events was 19% among BOS initiators and 4% among BOS continuers. One patient in each group developed oral candidiasis, while four BOS initiators (11%) developed esophageal candidiasis. Three BOS continuers had subnormal morning cortisol levels; while these were subclinical cases, they merit attention since long-term corticosteroids for EoE have been linked with possible hypothalamic–pituitary–adrenal axis suppression, the researchers noted.
In addition, while BOS initiators tended to maintain their endoscopic response, only 42% of those with an initial histologic response maintained a histologic response after 36 weeks of treatment or when leaving the study. Post hoc analyses confirmed that prolonged BOS treatment does not increase the chances of histologic or endoscopic response. Prior studies have suggested that EoE can become steroid-refractory over time and that certain molecular and histologic markers might predict resistance, the investigators noted.
Meritage Pharma (now part of Shire) was involved in the study design and conduct, data collection and management, and manuscript review. Dr. Dellon disclosed research funding from Meritage and Shire and a consulting relationship with Shire, along with ties to several other pharmaceutical companies. All six coinvestigators also disclosed ties to Meritage, Shire, or both, and two are Shire employees and stockholders.
*This story was updated on Feb. 7, 2019.
SOURCE: Dellon ES et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.051.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Budesonide oral suspension was well tolerated and maintained a histologic response in some patients with eosinophilic esophagitis.
Major finding: A total of 42% of initial histologic responders maintained a histologic response (less than 6 eosinophils per high-power field) after 24 weeks. Treatment was generally well tolerated, but 11% of initiators developed esophageal candidiasis.
Study details: Open-label extension study of a 12-week, multicenter, randomized, double-blind, placebo-controlled trial.
Disclosures: Meritage Pharma (now part of Shire) was involved in the study design and conduct, data collection and management, and manuscript review. Dr. Dellon disclosed research funding from Meritage and Shire and a consulting relationship with Shire, along with ties to several other pharmaceutical companies. All six coinvestigators also disclosed ties to Meritage, Shire, or both, and two are Shire employees and stockholders.
Source: Dellon ES et al. Clin Gastroenterol Hepatol. 2018 Jun 11. https://doi.org/10.1016/j.cgh.2018.05.051