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ORIGINAL ARTICLE
Year : 2014  |  Volume : 4  |  Issue : 5  |  Page : 34-38

Beta-interferon therapy in relapsing and remitting multiple sclerosis - challenges in an emerging country


1 Department of Neurology, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India
2 Department of Clinical Pharmacy, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India

Date of Web Publication19-Dec-2014

Correspondence Address:
Sureshkumar Radhakrishnan
Amrita Institute of Medical Sciences and Research Centre, PO - Ponekkara, Kochi - 682 041, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2231-0738.147464

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   Abstract 

Context: Multiple sclerosis (MS) is an immune-mediated demyelinating disease, with an increasing prevalence in India, as is seen in the recent studies. Beta-Interferon is the most widely used treatment option. There is a paucity of studies on beta-interferon in relapsing remitting multiple sclerosis (RRMS) in India. Aims: To study the efficacy, compliance, and side effect profiles of patients on beta-interferon, with a diagnosis of RRMS, and also look at other factors, such as, affordability, preference, and availability. Settings and Design: A retrospective-prospective design. Materials and Methods: Twenty patients with a diagnosis of RRMS were included in the study. They were followed up regularly while on beta-interferon. All patients underwent magnetic resonance imaging (MRI) of the brain, plain and contrast, and the expanded disability status scale (EDSS) score was assessed at regular intervals. Statistical Analysis Used: Data analysis was done using the SPSS 15.0 version. Results: The mean age was 36.25 ± 12.24 years, with a female:male ratio of 2.3:1. The majority were unemployed, and hence, were dependent on their families for treatment. There was a significant delay from diagnosis to start of interferon therapy, the mean duration being 29.95 months. Oligoclonal bands (OB) were positive in 70% of the subjects. Seventeen patients were on interferon beta 1a intramuscular and three patients on interferon beta 1a subcutaneous injections. The mean relapse rates per patient before and after starting beta interferon were 1.85 and 0.55 respectively. First dose fever was the most common side effect. Headache, myalgia, and psychiatric symptoms were also seen. Periventricular and juxtacortical lesions were the most common radiological sites. Conclusions: Beta-interferon is an effective and safe therapy in Indian patients with RRMS. However very few patients have been able to continue it as a long-term therapy, due to financial constraints.

Keywords: Beta-interferon, multiple sclerosis, relapsing remitting multiple sclerosis


How to cite this article:
Radhakrishnan S, Padmajan RK, Yadav PK, James E, Anandkumar A. Beta-interferon therapy in relapsing and remitting multiple sclerosis - challenges in an emerging country. Int J Nutr Pharmacol Neurol Dis 2014;4, Suppl S1:34-8

How to cite this URL:
Radhakrishnan S, Padmajan RK, Yadav PK, James E, Anandkumar A. Beta-interferon therapy in relapsing and remitting multiple sclerosis - challenges in an emerging country. Int J Nutr Pharmacol Neurol Dis [serial online] 2014 [cited 2020 Jan 28];4, Suppl S1:34-8. Available from: http://www.ijnpnd.com/text.asp?2014/4/5/34/147464


   Introduction Top


Multiple sclerosis (MS) is an immune-mediated chronic inflammatory and demyelinating illness affecting the central nervous system (CNS) in a relapsing-remitting or progressive course. Symptoms at disease onset are variable and include, visual and sensory abnormalities, motor dysfunction, ataxia, fatigue, and disturbances of the bladder and bowel function. In a majority (85%) of the cases of MS an acute episode is followed by a period of remission and is known as relapsing and remitting multiple sclerosis (RRMS). A chronic form of the illness due to natural disease progression is referred to as secondary progressive MS (SPMS).

A high prevalence of multiple sclerosis in India has been noted in the recent studies. Multiple sclerosis in India also has more involvement of the optic nerve and the spinal cord, according to many Indian studies. [1],[2],[3],[4] Interferon beta preparations are the most widely prescribed initial therapies for RRMS. Various studies around the world have shown its efficacy and also ability to reduce disease activity and relapses in RRMS. [5] There is only one study done in India on interferon-beta therapy, by Gupta et al. [6] In his prospective follow-up study, he showed that interferons were safe and effective in RRMS and secondary progressive MS.

The Mc Donald 2010 criteria [7] are used for diagnosis of the disease. As of now, MS is only a controllable disease. Acute relapses are managed by corticosteroids along with symptomatic management. Disease-modifying therapies (DMT) are the mainstay of treatment. At present, the Food and Drug Administration (FDA)-approved DMTs are the interferon-beta preparations - interferon beta 1a intramuscular/subcutaneous and interferon beta 1 b subcutaneous, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, and recently, dimethyl fumarate; the last two being oral therapies. The use of interferons in developing countries as a first-line treatment modality is limited by the high cost of these medications. To compound the problem, there are hardly any clinical studies done with patients on interferons in this population.

Hence, we undertook this study to look at the response of interferon-beta therapy on the Indian population, with regard to various problems, such as, the cost factor, compliance, availability, as well as direct drug-related factors like efficacy, side-effects, and tolerability.


   Materials and Methods Top


Aim of the study

To study the efficacy, compliance, and side effect profile of patients on beta-interferon, with a diagnosis of RRMS.

To look at patient-related factors, such as, choice of interferon based on affordability, number of injections, and working status.

Methodology

Twenty patients with a diagnosis of MS according to the Mc Donald's 2010 criteria, [7] specifically RRMS (according to International Survey Criteria, [8] being treated and followed up in the Multiple Sclerosis Clinic of Amrita Institute of Medical Sciences (AIMS), Kochi) were included in this retrospective-prospective study. The age of the patients included in the group was 18-60 years.

All the patients were followed up at 0-, 1-, and 12-month intervals and subsequently twice a year, with a fixed recommended dose of beta-interferon.

Seventeen patients were given interferon beta 1a, at dose of 30 mcg intramuscular per week, and three patients were on interferon beta 1 a subcutaneous, given at 44 mcg thrice a week. [9],[10]

All patients underwent an MRI of the brain, plain and contrast, at the initiation of the study and then at every 12-month intervals. Spine screening was not done in all patients.

The Kurtzke Expanded Disability Status Scale (EDSS) scoring [11] was done at the beginning and after one year of initiation of treatment and subsequently at 12-month intervals.

Patients who discontinued interferons were not followed up.

Informed consent was taken from the study participants.

An acute relapse was defined as an episode of neurological deficit that lasted for at least 24 hours and there was no other cause such as fever or infection contributing to it. [12]

Exclusion criteria

Patients with a diagnosis of Primary Progressive Multiple Sclerosis/Secondary Progressive Multiple Sclerosis were excluded from the study.

Multiple Sclerosis patients with severe disability EDSS > 6.5 were also excluded.

Pediatric and childhood MS were also not included.


   Results Top


Clinical profile

The mean age of the study group was 36.25 ± 12.24 years. Out of 20 patients, fourteen were females and six were males, with a female:male ratio of 2.3:1. The mean duration of the disease from the first onset of symptoms was 52.5 months ±40.3 (15 to 149) months.

The most common initial presentations were sensory symptoms or motor weakness in about half of the patients. Gait imbalance, cerebellar, and other brainstem symptoms were seen as the first symptoms in about 20% of the subjects. Oligoclonal bands were positive in 14 (70%).

Delay in treatment initiation and choice of interferons

The mean period from the first confirmed diagnosis to the start of interferon was 29.95 ± 34.095 months (range 1-108 months). Seventeen patients were on interferon beta 1a intramuscular and three were on interferon beta 1a subcutaneous injectables. The patients preferred injections, which were less frequent and had the least total monthly cost. The weekly once injection suited students and those who were employed, as they preferred to take injections during weekends.

The mean duration of treatment on beta-interferon was 17.45 ± 10.19 months (range 12-48 months) in the study population. The mean duration after starting beta interferon and to the last follow up in the clinic before the present analysis was almost two years (22.5 ± 10.26 months).

Treatment response

The mean relapse rate before starting beta-interferon was 1.85 (ranging from 1-5 relapses) and the mean relapse rate after starting interferon decreased to 0.55.

One-fourth (5/20) of the patients were on interferon for more than two years and the mean relapse rate in this group was 1.8. However, one out of these five patients had about five relapses.

The mean period from diagnosis to the start of beta-interferon was divided into early treatment group (<2 years) and late treatment group (>2 years). The total number of patients in the Early Treatment Group and Late Treatment Group were eleven and nine, respectively. Four patients in the Early Treatment Group had relapses. Two patients had a single relapse each, while the other two had two relapses each. In the Late Treatment Group only one patient had a relapse (A total of five episodes of relapses). Hence, a majority, that is, 15 patients were relapse-free when they were on interferon.

Socioeconomic issues

A majority (60%) of the study population was unemployed, most of them were homemakers, only 35% of them were employed, and one was self-employed. Sixty percent were married and received support from their family in taking the medications. Among the women who were married, approximately one-fourth of them conceived. As patients mostly bought medication on their own, without any external financial support, more than half of our study population were from cities and had a strong financial background. The annual income was more than Rupees 3 lakhs/year (5000 USD) in 35%, between 1-3 lakh/year in 40%, and less than 1 lakh/year (1700 USD) in 25% of the study population.

Imaging and disability

In our study, MRI brain imaging was done in all the patients at baseline and then every 12 months. MRI Spine was done in only 12 patients. EDSS scoring was done at baseline and at the 12-month follow-ups. MRI brain showed the most common lesions in the juxtacortical/subcortical and periventricular areas. Cervical, followed by dorsal spine, were the common locations for lesions in those who underwent spine imaging. [Table 1] shows the common sites of CNS involvement in the patients of RRMS. Only five patients had new T2-enhancing lesions and only two had contrast-enhancing lesions. Therefore, the radiological parameters showed good improvement in the study population.
Table 1: Common sites of CNS involvement in RRMS as evident from MRI (n=20)


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Expanded Disability Status Scale scoring was done at baseline and at the end of every 12 months. As this was a short study, only one patient showed progression from the baseline, from 4.0 to 5.0. This patient had five relapses while on interferon.

Side effects

Among patients treated with beta-interferon, first-dose fever was seen in all patients. Headache and myalgia were the next common side effects reported by the patients. Psychiatric symptoms were seen in 10% of the population [Table 2]. None had injection site reactions. The mean hemoglobin level in the study population was 13.2 mg/dl. Liver function tests showed elevation of Serum Glutamic Pyruvic Transaminase (SGPT) levels, more than twice, in only one patient.
Table 2: Adverse reactions to interferon in RRMS patients


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All of the patients were adherent to the treatment on evaluation by the Morisky medication adherence scale. [13]


   Discussion Top


Multiple Sclerosis is increasingly being recognized and diagnosed in the Indian population. [4],[14] Use of beta-interferon is becoming more frequent in clinical practice. There is only one study, by Gupta et al., [5] on the effect of beta-interferon on relapsing, remitting, and secondary progressive multiple sclerosis, in the Indian population.

In our study, we wanted to look into one of the most easily available disease-modifying therapies available in India and the challenges faced by patients and their relatives in taking interferon treatment as a long-term therapy. Demographic and social characteristics like employment, family support, and marital status were also studied.

The mean age and sex ratio of the patients affected in the study, their initial clinical presentation mostly as sensory, motor symptoms or visual loss were similar to other Indian and Asian studies. [1],[2],[3],[4] RRMS has a female predominance in India, as seen in other studies, [14],[15],[16] although male preponderance has been reported in few Indian studies. [4]

The National Institute of Health and Clinical Excellence (NICE) UK guidelines for MS recommend that the time from initial presentation to the first neurological evaluation be no longer than six weeks, with a further six weeks for any necessary investigations.

However, in developing countries, the delay in diagnosis and initiation of therapy can be substantial, as seen in our study. This can be due to a combination of factors like lack of MRI facilities, poor awareness about the existence of the disease among patients and to some extent physicians, and also economic issues.

Fernandez et al., [17] in a study from Spain revealed that the median time from onset of the first symptom to the first visit to a physician, was 19.2 months, and the time from the first symptom to confirmed diagnosis was 24.9 months (2.08 years). So, early diagnosis of MS is a problem in most parts of the world and more so in developing nations.

In a study by Goldberg et al., [18] comparing the cost-effectiveness for first-line treatment of relapsing and remitting MS, it was seen that IFN Beta 1 a subcutaneous injections, IFN Beta 1 b subcutaneous injections, and Glatiramer Acetate were the three most cost-effective disease-modifying therapies for the treatment of RRMS. However, in India, based on our study, patients preferred injection IFN Beta 1 a intramuscular more, because of the lower total cost per month and convenience of the once-a-week injection. This was also because patients pay for the treatment, as they have no insurance support.

Another major problem was woman unemployment. Kerala, the state where this study was done has one of the highest literacy rates in the country (93.9%). A study by Sebastian and Navaneetham [19] hypothesized that economic growth and education increased the rates of female work participation. However, in Kerala, where women's education is the highest, women have very poor work participation and unemployment among them is the highest among the major states of the country.

This paradox has a relevance in our study, as women with MS were mostly unemployed (60%) and they had to depend on their spouse or families for support. This is a hindrance for starting and also for being on long-term treatment. Most of them belonged to families with an annual family income less than Rupees 3 lakh per year (5000 USD), which is less than the cost of interferon therapy for a whole year.

However, the family support had a good psychological effect on these woman, as none of the married women were divorced, and those who were unmarried got support from their parents and siblings. None of the patients was living alone.

No patients stopped treatment because of intolerance. The side effect profiles were also comparable to those in other studies. [20] The side effects were mild and easily treatable. This was similar to other studies, which looked at drug safety. All patients in the study had first-dose fever and this needed to be explained to them before starting the therapy.

Cutaneous adverse events, that is, local injection site reactions were seen in 90% of the patients using subcutaneous formulations, while 33% in those were using intramuscular forms Balak et al. [21] However, none of the patients in our study developed these reactions and this was also seen in the study by Gupta et al. [6] Oligoclonal band positivity was comparable to other Indian and western studies. [22],[23]


   Conclusion Top


Our study shows that beta-interferon is an effective and safe therapy in Indian patients with RRMS. It reduces the number of relapses and disease progression, both clinically and radiologically. However, affordability is a key deterrent to initiation of interferons. The drug is mostly well-tolerated. One-fourth of the patients have stopped medications after one year citing financial constraints, in spite of getting good results from the therapy. Hence, once started, continuation is also a problem in many patients, on financial grounds. However, in spite of the small numbers, our study shows efficacy of interferons in Indian patients.

 
   References Top

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    Tables

  [Table 1], [Table 2]


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