Abstract Details

Title Combination Interferon-beta 1a and Mycophenolate Mofetil in Relapsing Remitting Multiple Sclerosis: Effects on Safety, Relapse Rate and Disability

Topic MS and Related Diseases

Presentation(s) P07 - (-)

Poster/Presentation
Number 123

Objective

Background BACKGROUND: Prior studies have suggested that adding MM to low-dose interferon result in improved clinical efficacy. To our knowledge, no study has evaluated MM added to IFN-?1a TIW (IFN).

Design/Methods DESIGN/METHODS: IRB-approved, investigator-initiated, randomized, 52-week, prospective, open-label phase-IIb trial, in which 29 2005 McDonald RRMS patients aged 18-65 were randomized to IFN from weeks 4-52 either 1) in combination with MM 2000mg daily from baseline to week 28 (IFN-MM; n=14), or 2) as monotherapy (n=15). EDSS, MSFC, MSQLI, Brain MRI, serum CBC and LFT's were collected at screening and week 52.

Results RESULTS: No significant between-group differences were found at baseline (INF-MM vs IFN) mean ± SD, median): Age 36.4±9.9, 42 vs. 41.3±10.9, 43; Female 60% vs. 46.7%; Caucasian 80% vs. 93%, EDSS 2.7±2.0, 2.5 vs. 3.1±1.1, 3.0. Three patients underwent early termination: IFN-MM: LFT >2x ULN (n=1), lost-to-follow-up (n=1); IFN (n=1) misdiagnosis of MS. Both groups maintained unchanged EDSS, T25FW, 9HPT and ARR over the study period. IFN arm PASAT improved (baseline: 43.5±9.7 vs. week-52:48.7±11.5; p=0.007), whereas PASAT remained unchanged with IFN-MM. Most common adverse events (AEs) included pain (n=12), headache (n=4), depression (n=4) and dizziness (n=4). Serious AEs included: IFN-MM: hypertension (1) and completed suicide (1)[ IFN injection site necrosis (1), tachycardia (1), suicidal ideation (1) and cholelithiasis (1); No significant between-group differences in AEs were found.

Conclusions CONCLUSIONS: Both IFN and IFN-MM demonstrated similar efficacy in preventing disability progression and maintaining low ARR. This pilot trial raises safety concerns for combination IFN-MM therapy. Serious adverse events occurred including death from suicide, highlighting the need for increased surveillance for mood disorders in this population. MSQLI, MRI results and MxA levels will be reported in a future publication.

Authors/Disclosures
Jacqueline A. Nicholas, MD (OhioHealth Riverside Methodist Hospital) PRESENTER	Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squib. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Greenwich Biosciences. Dr. Nicholas has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Nicholas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for EMD Serono. Dr. Nicholas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Vielo Bio. Dr. Nicholas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Nicholas has received research support from Novartis. The institution of Dr. Nicholas has received research support from Biogen. The institution of Dr. Nicholas has received research support from Genentech. The institution of Dr. Nicholas has received research support from PCORI. Dr. Nicholas has a non-compensated relationship as a Physician with National MS Society that is relevant to AAN interests or activities. Dr. Nicholas has a non-compensated relationship as a Physician with Siegal Rare Neuroimmune Association that is relevant to AAN interests or activities.
	No disclosure on file
Gavin Giovannoni, MD (QMUL)	Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche-Genentech. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Astoria Biologica. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape.
	No disclosure on file
	No disclosure on file
Colleen M. O'Connell, CNP (Ohio State University Medical Center)	No disclosure on file
Kottil W. Rammohan, MD (University of Miami)	Dr. Rammohan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Rammohan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Rammohan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Rammohan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Rammohan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. Dr. Rammohan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. The institution of Dr. Rammohan has received research support from Genentech. The institution of Dr. Rammohan has received research support from Genzyme. The institution of Dr. Rammohan has received research support from EMD Serono. The institution of Dr. Rammohan has received research support from Alexion.
	No disclosure on file
David Pitt, MD (Yale School of Medicine)	Dr. Pitt has nothing to disclose.
Michael K. Racke, MD (Quest Diagnostics)	Dr. Racke has received personal compensation for serving as an employee of Quest Diagnostics. Dr. Racke has or had stock in Quest Diagnostics.Dr. Racke has received intellectual property interests from a discovery or technology relating to health care.
Aaron L. Boster, MD (Ohiohealth)	Dr. Boster has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for sanofi. Dr. Boster has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for roche. Dr. Boster has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for novartis. Dr. Boster has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Dr. Boster has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Serono. The institution of Dr. Boster has received research support from Sanofi. The institution of Dr. Boster has received research support from Roche.

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