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Year : 2014  |  Volume : 62  |  Issue : 6  |  Page : 646--648

Mycophenolate mofetil in the treatment of multiple sclerosis: A preliminary report

Lekha Pandit, Sharik Mustafa, Chaithra Malli, Anitha D'Cunha 
 Department of Neurology, KS Hegde Medical Academy, Nitte University, Mangalore, Karnataka, India

Correspondence Address:
Lekha Pandit
Department of Neurology, KS Hegde Medical Academy, Nitte University, Mangalore-575 018, Karnataka


Background: Mycophenolate mofetil (MMF) is an affordable and tolerable drug reported to be beneficial in the treatment of multiple sclerosis (MS). Aim: To determine efficacy of MMF as first line disease modifying drug (DMD) in 40 patients with MS seen in our demyelinating disease registry. Materials and Methods: The annualized relapse rate (ARR) for 1 year prior to starting MMF therapy and 1 year post treatment was calculated. Pre- and post-treatment expanded disability status scores (EDSS), age at onset of treatment, disease duration, and type of MS were recorded. Wilcoxon rank sum test was used for comparison of ARRs and EDSS before and after treatment. Results: Forty patients included 27 females and 13 males. Mean duration of MMF therapy was 24 months (range 14-33 months). Pre-treatment mean ARR of 0.95 was significantly different from post treatment mean ARR of 0.11 (P = 0.0001). Pre-treatment mean EDSS 3.80 (inter quartile range [IQR] 3.5-4.5) was significantly different from post-treatment mean EDSS 2.66 (IQR 1.5-3.0, P = 0.0001). No adverse effects were reported that required stopping of medication. Five patients discontinued treatment 6-11 months after starting therapy, two of whom relapsed subsequently. Conclusion: Our preliminary results support the use of MMF, a cheap and well-tolerated drug, as first line disease modifying drug in MS. Long-term results in a larger patient cohort is required for validating our preliminary conclusions.

How to cite this article:
Pandit L, Mustafa S, Malli C, D'Cunha A. Mycophenolate mofetil in the treatment of multiple sclerosis: A preliminary report.Neurol India 2014;62:646-648

How to cite this URL:
Pandit L, Mustafa S, Malli C, D'Cunha A. Mycophenolate mofetil in the treatment of multiple sclerosis: A preliminary report. Neurol India [serial online] 2014 [cited 2020 Apr 4 ];62:646-648
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Full Text


Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the brain. The prevalence of MS has increased in recent times worldwide. India has transitioned from a low prevalence to medium prevalence zone for MS. [1],[2] It is recommended that disease modifying drugs (DMD) should be started in the early phase of the disease in order to improve disease course and delay progression. In western countries, approved first-line drugs include B-interferon and glatiramir acetate. In India, financial constraints encountered by patients restrict the large scale use of first line DMD. Therefore, there is a need for cost effective alternative drugs for the treatment of MS. Immunosuppressive drugs have not found favor as first line treatment. There have been no large scale trials to support the efficacy of drugs such as cyclophosphamide, azathioprine, or mycophenolate mofetil (MMF). They are not Food and Drug Authority (FDA) approved and hence off-label in the US. Nonetheless, immunosuppressive agents continue to be used in special situations when MS is refractory or as add on therapy with breakthrough relapses with conventional treatment. [3]

MMF selectively inhibits inosine 50-monophosphate dehydrogenase type II, responsible for de novo synthesis of the purine nucleotide guanine. It exerts profound immunosuppression on activated T and B cells and macrophages. MMF has been successfully used in a variety of autoimmune disorders including neurological disorders such as of polymyositis, chronic inflammatory demyelinating polyradiculoneuropathy, and multifocal motor neuropathy. [4],[5] A number of studies involving small patient numbers and with period of study ≤1 year have been reported. [6],[7],[8],[9],[10] An open-labeled study of relapsing remitting MS (RRMS) patients with a history of breakthrough disease activity after 6 months of interferon beta-1a (IFNB-1a) treatment received MMF as adjunctive therapy and the results suggested beneficial effects of combining MMF and IFNB in patients with poor response to IFNB alone. [6] Retrospective data also documented the safety profile of MMF alone or in combination with beta interferon or glatiramer acetate. [7],[8] A recent multicentric collaborative study from France found MMF used as a monotherapy had significant benefits in 344 patients studied. [11],[12] Our study is the first that looked at efficacy of MMF as monotherapy in patients who were treatment naοve for disease modifying therapy and in the Indian set-up.

 Materials and Methods

Forty patients were recruited from the Mangalore demyelinating disease registry. [13] Patients were diagnosed by Mc Donald criteria. [14] Inclusion criteria included inability to afford or those who discontinued first line DMD due to financial constraints, relapsing remitting or relapsing progressive disease, and at least one documented relapse/year for a minimum period of 2 years prior to the study The standard dose was 2 grams/day in twice daily doses. MMF is made available to all patients of the Mangalore demyelinating registry at subsidized rates.

Every patient's medical history including onset of disease, number of relapses, and disability were charted by either one of the authors, while disability progression as measured by Kurtzke's expanded disability score (EDSS) was documented in all cases by lead author. An MS relapse was defined as the appearance, reappearance, or worsening of symptoms of neurological dysfunction, lasting more than 24 hours.

The clinical efficacy was determined by comparing the annualized relapse rate (ARR) 1 year or more after starting MMF therapy with 1 year prior to starting therapy. Similarly, EDSS was scored 1 year prior, baseline, and 1 year after starting MMF therapy. Spontaneous reporting of adverse effects while on therapy were noted down in patient files. All patients had regular monitoring of blood counts including platelet counts, liver and renal functions at period intervals. Baseline evaluation excluded human immunodeficiency virus (HIV) and hepatitis B and C infection. All women in child-bearing age were counseled to maintain strict contraceptive measures. This study was approved by the Institutional ethics committee. All patients gave informed consent before study entry.

Statistical analysis

Statistical analysis was performed using statistical package of soial sciences (SPSS) version 20.0 (IBM corporation, Armonk, NY). Wilcoxon paired test was done to compare ARR and EDSS before and after MMF. All results are presented as mean ± SEM. Results were considered significant when P < 0.05.


Twenty-seven female and 13 male patients were included. There were 22 patients with relapsing-remitting multiple sclerosis (RRMS) and 18 with secondary-progressive multiple sclerosis (SPMS). Mean age at disease onset was 29.8 ± 9.2 and mean duration of illness was 7.3 ± 6.3 years [Table 1]. In seven patients, there was prior history of treatment with beta interferon. Patients were enrolled after a mean period of 2.7 years after stopping beta interferon (2.5-3.6 years) . In two patients, MMF was added due to break through relapses while on beta interferon, characterized by new clinical signs and newly enhancing lesions on magnetic resonance imaging (MRI). In the majority of patients (21), MMF was started in treatment naïve patients.{Table 1}

Mean duration of MMF therapy was 24 months (14-33 months). Pre-treatment mean ARR of 0.95 ± 0.6 was significantly different from post treatment mean ARR of 0.11 ± 0.3 (P = 0.0001). Pre-treatment EDSS mean 3.80 (inter quartile range [IQR] 3.5-4.5) was significantly different from post treatment mean EDSS 2.66 (IQR 1.5-3.0); P = 0.0001). Two patients reported hand tremors, 11 patients complained of mild hair loss while on therapy but all 13 patients remained drug compliant. Five patients discontinued treatment 6-11 months after starting therapy, two of whom relapsed subsequently. Both patients who received combination therapy with beta interferon and mycophenolate remained well. They discontinued beta interferon after remaining asymptomatic for 1 year (contrast MRI brain and spine showing no new lesions) and remained well on monotherapy with MMF.


Mycophenolate mofetil is an immunosuppressant more popularly used in preventing graft rejection. Long-term safety and tolerability data are lacking though the drug is found to be increasingly useful in a variety of autoimmune disorders. In the west, it has found a selective use in treatment of refractory MS. Both of our patients in this series who had breakthrough relapses while on beta interferon did well on combination therapy. In developing countries, its main usefulness may be as a cheap and reliable alternative to first line and expensive DMD. In our prospective study, the clinical efficacy of MMF in a predominantly treatment naïve cohort of MS patients was evaluated. There was significant improvement in clinical endpoints of efficacy namely annualized relapse rate and disability assessed by EDSS. The drug was well-tolerated with minor side effects which did not interfere with drug compliance. Our study showed the safety and clinical efficacy of a relatively cheap oral agent in the treatment of MS. It may be used in treatment naïve patients and also in treatment refractory MS with good effect. Our study as well as others. [7] have also shown its effectiveness in secondary progressive MS with superimposed relapses. Though our preliminary results are promising, the results of this study need to be replicated in a larger cohort and long term data on safety and tolerability need to be obtained.


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