Article:Ralf G., Ludwig K., Douglas L. A., Amit B., & Gavin G., et al.(2012). Placebo-Controlled Phase 3 Study of Oral BG-12 for RelapsingMultiple Sclerosis. TheNew England Journal of Medicine.367 pp 1098-1107. DOI: 10.1056/NEJMoa1114287
Theaim of the study was to establish the effectiveness of Oral dimethylfumarate (BG-12) in the management of multiple sclerosis. Severalstudies have confirmed that one of the major pathological factorsthat influence the development of multiple sclerosis is theinflammation and oxidation associated with stresses, which results inneurodegeneration. During preclinical studies, dimethyl fumarateshowed some positive impacts on “neuroinflammation,neurodegeneration, and toxic oxidative stress”. It was establishedthat BG-12 might act by activation of antioxidant response pathwaysor modulating immune cell responses. This study involved a clinicalstudy on the effectiveness of BG-12 (Ralf et al., 2012).
Theparticipants were included or excluded in the investigation dependingon predetermined criteria. The selection criterion was based on age,EDSS score, disease activity, and relapse based on Mcdonald criteria.For example, patients were included if they were aged between 18 and55 years, had a score of 0 to 5.0 on the EDSS and a documentedevidence of disease activity. Patients were excluded if the diseasewas progressive form, the existence of another major condition,abnormal diagnostic results, or incidences of contraindicatedmedication in the recent past (Ralf et al., 2012).
Wasthere a control group
Therewas a control group in the study. Out of the all the participantsincluded in the randomized study, 410 patients were selected to bedosed with placebo. 317 of them completed the study (Ralf et al.,2012). Placebos are medically ineffective drugs or interventionsthat are intended to deceive the patient. They care used in clinicaltrials as controls, although there are medical and research ethicsissues associated with the use of placebos (Hernandez, 2014).
Allthe selected participants, in different sites located in 28 nations,were randomly chosen in a “double-blind fashion” and received aBG-12 at 240 mg twice a day, 240 mg three times a day and placebo forthe first, second and third group respectively. An equal number ofpatients, in all sites, were allocated to one of the three groups.Different neurologists were responsible for every aspect of the studyto ensure that the interventions remained concealed. For example,neurologists involved in treatments did not participate in theassessment (Ralf et al., 2012).
Theefficacy of the BG-12 was determined by the relapse of multiplesclerosis within two years after the dose. It was established thatthe number of relapses in both BG-12 groups (BID and TID) wererelatively lower compared to the group administered with placebo. InBID and TID groups, the number of relapses was 27 percent and 26percent respectively compared 46 percent in the placebo patients.Additionally, the drug reduced the progression of disability with to16 to 18 percent compared to 27 percent in the placebo participants.It also significantly reduces hyperintense lesions on T2 weightedimages. This indicates that Oral dimethyl fumarate is active in themanagement of multiple sclerosis (Ralf et al., 2012).
Theresult of the study shows that BG-12 can significantly reducerelapses among multiple sclerosis patients as well as the progressionof disability. Despite reported cases of gastrointestinal events insome patient, the adverse effects of the drug were acceptable,ranging from mild to moderate severity (Ralf et al., 2012).
Thereare some aspects of Oral dimethyl fumarate clinical trials that werenot included in this study. They can form the basis of futureinquiries on the effectiveness of the drug. This includes head tohead comparison with approved therapies to compare its efficacy andsafety. It is also important to establish the immunomodulatorymechanisms that are responsible for Oral dimethyl fumarate therapy infuture clinical studies (Ralf et al., 2012).
Hernandez,A. (2014). The Definition of Placebo in the Informed Consent Forms ofClinical Trials. PLoSONE 9(11):e113654. doi:10.1371/journal.pone.0113654
RalfG., Ludwig K., Douglas L. A., Amit B., & Gavin G., et al. (2012).Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing MultipleSclerosis. TheNew England Journal of Medicine.367 pp 1098-1107. DOI: 10.1056/NEJMoa1114287.