OBJECTIVE: To determine the safety and efficacy of roquinimex (linomide) in the management of relapsing-remitting and secondary progressive MS as monitored by MRI. BACKGROUND: Preclinical studies and several short term randomized trials of linomide suggested clinical and MRI-measured benefits with acceptable risk for closely followed MS patients. METHODS: The North American Linomide Trial formally screened 853 individuals for relapsing or secondary progressive, clinically definite MS; recent disease activity or progression; and an Expanded Disability Status Scale score at entry of 3.0 to 6.5 inclusive. MRI was obtained on 811 subjects at pre-enrollment, 718 cases at enrollment, and then at three monthly intervals until the trial was prematurely terminated for unacceptable toxicity. RESULTS: Enhancement was found on 40.2% of 718 entry scans. Statistically robust correlations were found between clinical demographic data and several entry MRI measures including CSF volume, a reflection of brain atrophy. Assessment of the effect of treatment on MRI-measured disease was limited by early trial termination. However, active treatment for 3 months reduced the proportion of patients with one or more enhancements. An exploratory analysis suggested that 2.5 mg was the most active of three doses tested in limiting the total volume of enhanced tissue, the proportion of MRI-defined lesions designated as "black holes," and by a novel MRI composite disease measure. CONCLUSIONS: The short term signature of the effect of linomide on MRI-measured aspects of the disease suggests that safer drugs of this class might be useful in the management of MS. The use of a composite index of the heterogeneous nature of the pathology of MS as captured by MRI may have merit as an outcome measure in clinical trials.
RCT Entities:
OBJECTIVE: To determine the safety and efficacy of roquinimex (linomide) in the management of relapsing-remitting and secondary progressive MS as monitored by MRI. BACKGROUND: Preclinical studies and several short term randomized trials of linomide suggested clinical and MRI-measured benefits with acceptable risk for closely followed MS patients. METHODS: The North American Linomide Trial formally screened 853 individuals for relapsing or secondary progressive, clinically definite MS; recent disease activity or progression; and an Expanded Disability Status Scale score at entry of 3.0 to 6.5 inclusive. MRI was obtained on 811 subjects at pre-enrollment, 718 cases at enrollment, and then at three monthly intervals until the trial was prematurely terminated for unacceptable toxicity. RESULTS: Enhancement was found on 40.2% of 718 entry scans. Statistically robust correlations were found between clinical demographic data and several entry MRI measures including CSF volume, a reflection of brain atrophy. Assessment of the effect of treatment on MRI-measured disease was limited by early trial termination. However, active treatment for 3 months reduced the proportion of patients with one or more enhancements. An exploratory analysis suggested that 2.5 mg was the most active of three doses tested in limiting the total volume of enhanced tissue, the proportion of MRI-defined lesions designated as "black holes," and by a novel MRI composite disease measure. CONCLUSIONS: The short term signature of the effect of linomide on MRI-measured aspects of the disease suggests that safer drugs of this class might be useful in the management of MS. The use of a composite index of the heterogeneous nature of the pathology of MS as captured by MRI may have merit as an outcome measure in clinical trials.
Authors: Fred D Lublin; Stacey S Cofield; Gary R Cutter; Tarah Gustafson; Stephen Krieger; Ponnada A Narayana; Flavia Nelson; Amber R Salter; Jerry S Wolinsky Journal: Mult Scler Relat Disord Date: 2017-09-23 Impact factor: 4.339
Authors: Jennifer Moodie; Brian C Healy; Guy J Buckle; Susan A Gauthier; Bonnie I Glanz; Ashish Arora; Antonia Ceccarelli; Shahamat Tauhid; Xue-Mei Han; Arun Venkataraman; Tanuja Chitnis; Samia J Khoury; Charles R G Guttmann; Howard L Weiner; Mohit Neema; Rohit Bakshi Journal: J Neurol Sci Date: 2011-12-28 Impact factor: 3.181
Authors: Per Soelberg Sørensen; Giancarlo Comi; Timothy L Vollmer; Xavier Montalban; Ludwig Kappos; Yuval Dadon; Tali Gorfine; Maya Margalit; Nissim Sasson; Svetlana Rubinchick; Volker Knappertz Journal: Int J MS Care Date: 2017 Jan-Feb
Authors: Carmen Tur; Marcello Moccia; Frederik Barkhof; Jeremy Chataway; Jaume Sastre-Garriga; Alan J Thompson; Olga Ciccarelli Journal: Nat Rev Neurol Date: 2018-01-12 Impact factor: 42.937
Authors: Fred D Lublin; Stacey S Cofield; Gary R Cutter; Robin Conwit; Ponnada A Narayana; Flavia Nelson; Amber R Salter; Tarah Gustafson; Jerry S Wolinsky Journal: Ann Neurol Date: 2013-03-11 Impact factor: 10.422