E O Meltzer1, P Chervinsky2, W Busse3, K Ohta4, P Bardin5, D Bredenbröker6, E D Bateman7. 1. Department of Pediatrics, Division of Allergy and Immunology, University of California, San Diego, CA, USA. Electronic address: eliomeltzer@gmail.com. 2. Northeast Medical Research Associates, Dartmouth, MA, USA. Electronic address: pchervinsky@gmail.com. 3. Division of Allergy and Immunology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. Electronic address: wwb@medicine.wisc.edu. 4. Department of Respiratory Medicine and Allergology, Tokyo National Hospital, Tokyo, Japan. Electronic address: kenohta@tokyo-hosp.jp. 5. Monash Lung & Sleep, Monash Medical Center and University, Melbourne, Australia. Electronic address: philip.bardin@monash.edu. 6. Takeda Pharmaceuticals International GmbH, Zurich, Switzerland. Electronic address: dirk.bredenbroeker@takeda.com. 7. Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South Africa. Electronic address: Eric.Bateman@uct.ac.za.
Abstract
BACKGROUND: The role of roflumilast as a potential asthma treatment is not yet fully understood. A series of placebo-controlled trials were undertaken in order to investigate the safety and efficacy of roflumilast in asthma. AIM: To evaluate the efficacy of roflumilast in nine randomized proof-of-concept, placebo-controlled monotherapy and combination therapy phase II and III clinical studies performed between 1997 and 2005. METHODS: The studies were conducted at sites in Europe, North and South America, Africa, Australasia and Asia and study length varied from 4 to 24 weeks. Data were analyzed from 4873 patients, 12-70 years of age, of whom 2668 receivedroflumilast. At randomization patients had a forced expiratory flow (FEV1) of 45-90%. Roflumilast was investigated at doses of 125, 250 and 500 μg versus placebo. In two studies, 500 μg roflumilast was added on top of standard therapy with inhaled corticosteroids (ICS), 250 μg fluticasone propionate, or 400 μg beclomethasone dipropionate (BDP). Improvement in FEV1 from baseline was the primary endpoint in seven studies. Key secondary endpoints included asthma symptom scores and time to first severe exacerbation. RESULTS:Roflumilast consistently improved FEV1 across the nine studies compared with placebo, reaching statistical significance in three studies. When given in addition to ICS, roflumilast provided additional improvements in FEV1 which was statistically significant for 500 μg roflumilast/400 μg BDP versus placebo/400 μg BDP. CONCLUSION: Together these studies show that roflumilast has potential as an effective anti-inflammatory therapy for the treatment of asthma. Additional beneficial effects are observed when given in combination with ICS, which warrant further investigation. All studies were funded by Takeda. Trial registration numbers available on ClinicalTrials.gov: NCT00073177, NCT00076076, NCT00163527.
RCT Entities:
BACKGROUND: The role of roflumilast as a potential asthma treatment is not yet fully understood. A series of placebo-controlled trials were undertaken in order to investigate the safety and efficacy of roflumilast in asthma. AIM: To evaluate the efficacy of roflumilast in nine randomized proof-of-concept, placebo-controlled monotherapy and combination therapy phase II and III clinical studies performed between 1997 and 2005. METHODS: The studies were conducted at sites in Europe, North and South America, Africa, Australasia and Asia and study length varied from 4 to 24 weeks. Data were analyzed from 4873 patients, 12-70 years of age, of whom 2668 received roflumilast. At randomization patients had a forced expiratory flow (FEV1) of 45-90%. Roflumilast was investigated at doses of 125, 250 and 500 μg versus placebo. In two studies, 500 μg roflumilast was added on top of standard therapy with inhaled corticosteroids (ICS), 250 μg fluticasone propionate, or 400 μg beclomethasone dipropionate (BDP). Improvement in FEV1 from baseline was the primary endpoint in seven studies. Key secondary endpoints included asthma symptom scores and time to first severe exacerbation. RESULTS:Roflumilast consistently improved FEV1 across the nine studies compared with placebo, reaching statistical significance in three studies. When given in addition to ICS, roflumilast provided additional improvements in FEV1 which was statistically significant for 500 μg roflumilast/400 μg BDP versus placebo/400 μg BDP. CONCLUSION: Together these studies show that roflumilast has potential as an effective anti-inflammatory therapy for the treatment of asthma. Additional beneficial effects are observed when given in combination with ICS, which warrant further investigation. All studies were funded by Takeda. Trial registration numbers available on ClinicalTrials.gov: NCT00073177, NCT00076076, NCT00163527.
Authors: Anne E Dixon; Kathryn V Blake; Emily A DiMango; Mark T Dransfield; Laura C Feemster; Olivia Johnson; Gem Roy; Heather Hazucha; Jean Harvey; Meredith C McCormack; Robert A Wise; Janet T Holbrook Journal: Obes Sci Pract Date: 2021-05-25
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Authors: Byung Keun Kim; So Young Park; Ga Young Ban; Mi Ae Kim; Ji Hyang Lee; Jin An; Ji Su Shim; Youngsoo Lee; Ha Kyeong Won; Hwa Young Lee; Kyoung Hee Sohn; Sung Yoon Kang; So Young Park; Hyun Lee; Min Hye Kim; Jae Woo Kwon; Sun Young Yoon; Jae Hyun Lee; Chin Kook Rhee; Ji Yong Moon; Taehoon Lee; So Ri Kim; Jong Sook Park; Sang Heon Kim; Heung Woo Park; Jae Won Jeong; Sang Hoon Kim; Young Il Koh; Yeon Mok Oh; An Soo Jang; Kwang Ha Yoo; You Sook Cho Journal: Allergy Asthma Immunol Res Date: 2020-11 Impact factor: 5.764