| Reference | [1]. N Engl J Med. 2020 Jul 16;383(3):229-239. doi: 10.1056/NEJMoa2000073.<br />
Trial of Roflumilast Cream for Chronic Plaque Psoriasis.<br />
Lebwohl MG(1), Papp KA(1), Stein Gold L(1), Gooderham MJ(1), Kircik LH(1), Draelos ZD(1), Kempers SE(1), Zirwas M(1), Smith K(1), Osborne DW(1), Trotman ML(1), Navale L(1), Merritt C(1), Berk DR(1), Welgus H(1); ARQ-151 201 Study Investigators.<br />
Collaborators: Adam DN, Albrecht LE, Alonso-Llamazares J, Bruce S, Draelos ZD, Ferris LK, Forconi RJ, Gooderham M, Hong CH, Jones TM, Kempers SE, Kircik LH, Lebwohl MG, Lee MS, Lee P, Loo WJ, Lynde C, Madkan V, Nahm W, Osman L, Papp K, Pariser DM, Sapra S, Stein Gold L, Stewart DM, Stoll D, Toth DP, Tyring S, Wiseman MC, Zirwas MJ.<br />
Author information: (1)From the Icahn School of Medicine at Mount Sinai, New York (M.G.L., L.H.K.); Probity Medical Research and K. Papp Clinical Research, Waterloo (K.A.P.), and the SkiN Centre for Dermatology, Probity Medical Research and Queen's University, Peterborough (M.J.G.) – both in Ontario, Canada; Henry Ford Medical Center, Detroit (L.S.G.); Indiana Medical Center, Indianapolis (L.H.K.); Physicians Skin Care and DermResearch, Louisville, KY (L.H.K.); Dermatology Consulting Services, High Point, NC (Z.D.D.); Minnesota Clinical Study Center, Fridley (S.E.K.); Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley (M.Z.); and Arcutis Biotherapeutics, Westlake Village (K.S., D.W.O., L.N., C.M., D.R.B., H.W.), and ML Trotman Consulting, Newbury Park (M.-L.T.) – both in California.<br />
Comment in Ann Intern Med. 2020 Nov 17;173(10):JC55.<br />
BACKGROUND: Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis. METHODS: In this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator's global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a score of 0 indicates clear, 1 almost clear, and 4 severe). Secondary outcomes included an IGA score indicating clear or almost clear plus a 2-grade improvement in the IGA score for the intertriginous area and the change in the Psoriasis Area and Severity Index (PASI) score (range, 0 to 72, with higher scores indicating worse disease). Safety was also assessed. RESULTS: Among 331 patients who underwent randomization, 109 were assigned to roflumilast 0.3% cream, 113 to roflumilast 0.15% cream, and 109 to vehicle cream. An IGA score indicating clear or almost clear at week 6 was observed in 28% of the patients in the roflumilast 0.3% group, in 23% in the roflumilast 0.15% group, and in 8% in the vehicle group (P<0.001 and P = 0.004 vs. vehicle for roflumilast 0.3% and 0.15%, respectively). Among the approximately 15% of patients overall who had baseline intertriginous psoriasis of at least mild severity, an IGA score at week 6 indicating clear or almost clear plus a 2-grade improvement in the intertriginous-area IGA score occurred in 73% of the patients in the roflumilast 0.3% group, 44% of those in the roflumilast 0.15% group, and 29% of those in the vehicle group. The mean baseline PASI scores were 7.7 in the roflumilast 0.3% group, 8.0 in the roflumilast 0.15% group, and 7.6 in the vehicle group; the mean change from baseline at week 6 was -50.0%, -49.0%, and -17.8%, respectively. Application-site reactions occurred with similar frequency in the roflumilast groups and the vehicle group. CONCLUSIONS: Roflumilast cream administered once daily to affected areas of psoriasis was superior to vehicle cream in leading to a state of clear or almost clear at 6 weeks. Longer and larger trials are needed to determine the durability and safety of roflumilast in psoriasis. (Funded by Arcutis Biotherapeutics; ARQ-151 201 ClinicalTrials.gov number, NCT03638258.).<br />
DOI: 10.1056/NEJMoa2000073 PMID: 32668113 [Indexed for MEDLINE]<br />
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[2]. Neurosci Lett. 2020 Sep 25;736:135281. doi: 10.1016/j.neulet.2020.135281. Epub 2020 Jul 28.<br />
Roflumilast: A potential drug for the treatment of cognitive impairment?<br />
Sugin LJS(1), Murugesan A(2), Bindu M(3), Sunil KN(4).<br />
Author information: (1)Department of Pharmacology, Siddha Central Research Institute, Central Council for Research in Siddha, Ministry of AYUSH, Govt. of India, Anna Govt. Hospital Campus, Arumbakkam, Chennai-106, India. (2)Department of Neurology, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Gorimedu, Puducherry, India. (3)Department of Psychiatry, Srivenkatesheswaraa Medical College, Puducherry, India. (4)Department of Neurology, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Gorimedu, Puducherry, India. Electronic address: [email protected].<br />
Phosphodiesterase-4 regulates the intracellular level of cAMP. Roflumilast, a selective PDE-4 inhibitor was the first agent in this class to have reached the market for patients with chronic obstructive pulmonary disease worldwide. Numerous preclinical evidences indicate the role of PDE-4 inhibitors in reversal of ageing-related alterations induced in animal models by various pharmacological agents, overexpression of mutant forms of human amyloid precursor proteins and in aging, as well. Roflumilast was capable of decreasing PDE-4B and 4D subtypes with an increase in the expression of pCREB and BDNF in hippocampus of rats. The beneficial effects of roflumilast on cognition are believed to be mediated through the above-mentioned cellular effects. Recently, Jabaris et al had shown that roflumilast has improved the short and long-term memory in rodents. Several lines of evidence indicate that targeting PDE-4 inhibition might offer novel approaches in the treatment of age-associated memory impairment and in Alzheimer's disease. Likewise, in a recent report, roflumilast improved the memory functions in humans after administration of 100 μg of the drug, without the typical side effects of PDE-4 inhibitors, which might offer a novel therapeutic option for the treatment of cognitive impairment and Alzheimer disease. In the current article, the author reviews the most recent evidences demonstrating the beneficial effects of roflumilast on learning and memory in animal models and humans.<br />
DOI: 10.1016/j.neulet.2020.135281 PMID: 32735939 [Indexed for MEDLINE]<br />
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[3]. Roflumilast.<br />
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. 2018 Jun 4.<br />
Roflumilast is a selective inhibitor of phosphodiesterase-4 (PDE-4) that has unique antiinflammatory activity and is used to treat and prevent exacerbations of chronic obstructive pulmonary disease (COPD). Roflumilast has not been linked to significant serum enzyme elevations during therapy or to instances of clinically apparent acute liver injury.<br />
PMID: 31643522<br />
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[4]. Roflumilast.<br />
Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006–. 2020 May 11.<br />
No information is available on the use of roflumilast in nursing mothers. The drug and its metabolite are more than 97% bound to plasma proteins, so amounts in milk are likely to be very low. However, the manufacturer states that the drug should not be used by women who are nursing.<br />
PMID: 32352702<br />
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[5]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Aug 12;43(8):698-701. doi: 10.3760/cma.j.cn112147-20190721-00523.<br />
[Research progress of roflumilast in the treatment of bronchial asthma].<br />
[Article in Chinese; Abstract available in Chinese from the publisher]<br />
Chen RN, Zhu L.<br />
DOI: 10.3760/cma.j.cn112147-20190721-00523 PMID: 32727185 [Indexed for MEDLINE]
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