Tag: India

Can we afford not to afford treatment of multiple sclerosis in India?

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Can we afford not to afford treatment of multiple sclerosis in India?
Neha Pandita 1, MD, Anuradha Batra 1, MD, Prahlad K Sethi 1, MD, Nitin K Sethi 2, MD

1 Department of Neurology, Sir Ganga Ram Hospital, New Delhi (India)
2 Department of Neurology, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, NY (U.S.A.)

 

Multiple sclerosis (MS) is a chronic neurological disease which affects men and women in the prime of their youth. The disease can present in relapsing-remitting, secondary progressive, progressive relapsing and primary progressive forms and leads to increasing disability during the course of the patient’s lifespan. Symptoms such as muscle weakness, gait and balance problems, coordination problems, visual impairment, diplopia, bladder and bowel disturbances, sensory symptoms, cognitive dysfunction and fatigue can be disabling at times and lead to poor health related quality of life, neurological disability and high health care costs. Progressive disease can be paricularly disabling leading to a wheel chair chair dependent on caregivers for activities of daily living. In India; till a few years ago, MS was thought to be rare and a disease of the Western hemispher. It is unclear why now we are seeing more and more MS patients in India. Is it because with advances in health care and diagnostics, we are diagnosing more cases which earlier remained undiagnosed or is the incidece of this disease actually increasing in the Indian population? This still needs to be determined and it would behoove us well to start a national MS registry and keep a track of MS cases and coregister with dietary and enviromental variables. Many low and middle income countres such as India have a huge population with limited accessibility and affordability to health care facilities. About 70% of India’s 1.3 billion population lives in rural areas with 30% living below the poverty line. In a country like India, a disease like MS can have a particularly devastating impact not just because of its chronicity and propensity to affect the young but also due to its high treatment cost burden. A study published in April, 2015 found that the cost of first generation disease modifying medications for MS increased from between $8000 to $11000 annually in the 1990s to approximately between $60000 to S90000 per year currently. Newer disease modifying MS drugs cost even more.In the west, patients with MS commonly pay for their MS treatment in one of the following ways:

1. Job (employer) based health insurance plan
2. Individual health insurance plan
3. Medicare
4. Medicaid or state children’s health insurance program
5. Other state and federal government funded programs for the uninsured and underinsured

In India, where illiteracy, unemployment and poverty remain major social problems, state and federal supported health insurance schemes benefit only a small fraction of the population. As in India at present there is no National Health Insurance program, patients have to pay out of pocket for health care. The purpose of writing this commentary is to draw attention to the cost burden associated with a chronic disease like MS and start a discussion on treatment solutions that may benefit our MS population without causing unbearable financial burden.
We calculated the average health care cost to a patient who is first time admitted for any demyelinating disease, in a corporate health care institution. A patient with spastic paraparesis was admitted to Sir Ganga Ram Hospital (SGRH) with provisional diagnosis of acute myelitis later confirmed as MS. We found that the entire hospitalization cost him around Rs. 1.8 lac ($2560).

Breakdown of costs:

Investigations:
–contrast enhanced MRI brain and cervical spine (Rs. 26000/ $ 416)
–visual evoked potential (VEP) (Rs. 2000/$ 32 )
–lumbar puncture (CSF analysis) (Rs. 8000/ $ 128)
–ancillary investigations like autoimmune encephalitis panel (Rs. 40000/ $ 464).
Treatment costs:
—pulse IV steroid therapy x 5 days (Rs. 70000/ $ 1120)
Hospital stay costs:
–room cost plus ancillary expenditure (Rs. 70000/ $ 1120)

It is important to remember that this is the financial burden borne out of pocket by an average middle class patient admitted to SGRH. Patients who live below the poverty line cannot afford such costs and the financial burden forces family members to take loans or at times sell their home and property to pay for the treatment. Unlike a case of post infectious myelitis, a patient with MS may suffer an acute exacerabation or relapse leading to another hospitalization and additional costs. The various MS disease modifying agents are so expensive that few patients in India can afford the drugs. Many as a result discontinue treatment regimens and self medicate with medications such as oral steroids.

We also calculated the average cost to the patient of various disease modifying agents available in India.

1. Injectable DMTs like Avonex (beta interferon) given at a dose of 30mcg I/M once a week costs Rs. 30000/ $ 480 dollars monthly.
2. Copaxone (glatiramer acetate) Rs. 20000/ $ 320 monthly.
3. Mitoxantrone Rs. 400/ $ 5 per vial
4. Tysabri (natalizumab) costs a whopping Rs. 1,40,800/ S 2184 monthly.
5. Oral DMTs like fingolimod costs around Rs. 3,00,000/ S 4790 dollar for 30 capsules, teriflunomide Rs. 2,90,000/ $ 4500 for 1 month supply, and dimethyl fumarate Rs. 3,40,000/ $ 5300 for 1 month supply.
6. Azathioprine costs Rs. 600/ $ 9.6 per month

The per capita income in India is estimated at just short of Rs. 6000 per month which equals $ 90 per month. That means the per capita income for a family of 4 would be less than $ 400 a month, but the reality is that most people live on much less than that and struggle to provide for the basic needs of food, clothing and shelter. Both the interferons and the oral DMTs are accessible to only a few in India due to their exorbant cost. As a result, many Indian MS patients cannot afford treatment and are left behind untreated with significant neurological disability impairing their quality of life. In India, where it is estimated that around 100,000-200,000 people have MS, finding cost effective treatment options is very important.

What are the solutions?

1. Methylprednisolone (Solumedrol) is an effective drug used to treat an acute attack of MS. Once the diagnosis of MS is confirmed, and patient presents to the hospital with an acute exacerbation, first dose of methylprednisolone can be administered in the emergency department followed by rest of the doses at home. The outpatient administration can be carried out by trained nurses via patient outreach programs. This will greatly reduce the cost of treating an acute attack of MS without requiring admission.

2. An initial MS diagnostic and treatment package should be constituted, including all the necessary initial investigations and treatment. This shall help drive down the initial costs incurred by patients and family members.

3. A MRI package should be constituted. This should include the cost of MRI brain and cervical spine imaging at least once a year and help in reducing the diagnostic cost associated with repeated neuroimaging in patients with MS.

4. A National Health Insurance scheme geared towards chronic neurological diseases such as MS should be formulated. While many good insurance schemes have been recently launched by the government, unfortunately they remain on paper only.

5. Pharmaceutical companies manufacturing and marketing MS drugs should be approached by the government and the cost of MS drugs should be negotiated so that more patients can afford these medications and avail their benefits. Recently 3 Indian pharaceutical companies have launched generic versions of Tecfidera (dimethyl fumarate) costing under Rs.4000/month. Intas pharmaceuticals generic version of Aubagio (teriflunomide) costs only Rs. 2000/month.

6. There are various studies documenting the effectiveness of azathioprine in MS patients. A multicentre randomized non inferiority trial was conducted comparing azathioprine vs beta interferons for relapsing remitting multiple sclerosis and it was found that efficacy of azathioprine is not inferior to that of beta interferon for patients with relapsing remitting multiple sclerosis 1. Massacesi et al conducted a study evaluating the efficacy of azathioprine therapy on new brain lesions evaluated using magnetic resonance imaging and concluded that azathioprine administered at lymphocyte suppressing doses, is effective in reducing MS new brain inflammatory lesions and is well tolerated 2. In a study by Casetta et al in 698 patients with MS, it was concluded that azathioprine is a fair alternative to interferon beta for treating MS patients 3. In SGRH, we have around 20 patients with MS who are on azathioprine for the past 10 years, doing well and tolerating the medication well. Considering the convenience of oral administration, low cost and good efficacy, azathioprine may represent an alternative to interferon and oral DMTs. This should be studied further in the Indian context.

Conclusions

In India, there is a large unmet disease burden of MS. We can’t afford not to afford the treatment of MS in India as it affects our young population who are the backbone of our nation. To tailor to the requirements of the Indian population, drug trials with large sample size using cheaper drugs such as azotioprine are needed. Large academic medical centers in India should take the lead in this initiative and run head to head trials of azothioprine against more established injectables and oral DMTs.

Outpatient acute seizure management at the level of the general practitioner clinic: a proposed treatment algorithm

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Outpatient acute seizure management at the level of the general practitioner clinic: a proposed treatment algorithm

 

Prahlad K Sethi, MD1 Dhrumil Shah, MD1 Anuradha Batra, MD 1 Nitin K Sethi, MD2

 

1 Department Neurology, Sir Ganga Ram Hospital, New Delhi, India

2 Department of Neurology, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, NY (U.S.A.)

 

 

Seizures beget seizures has been a point of contention over the years. There is some scientific evidence to suggest that each seizure increases the risk for future seizures and that failure to control seizures in a timely fashion can lead to status epilepticus (SE). Status epilepticus is a life threatening neurological emergency which can present as an exacerbation of a pre-existing seizure disorder such as in an epilepsy patient who is non-compliant with his anti-epileptic drug (AED) regimen or as the initial manifestation of a seizure disorder (epilepsy) or as the manifestation of other systemic and cerebral insults. Prolonged seizures are also associated with worse neurological outcomes. With the aim to reduce the time to treatment gap, outpatient treatment of seizures is now been explored. We discuss this approach in relation to the health care system of India.

 

General practitioners (GPs) also referred to as primary care physicians (PCPs) form the backbone of the Indian health care delivery system. Usually, they are in solo practice working in small clinics (offices) which are ill-equipped to handle medical and surgical emergencies such as seizures and SE.

As awareness about coronary artery disease has increased, GPs now feel comfortable administering aspirin and nitrates before transferring the patient to the hospital. With respect to emergency management of seizures, their knowledge and experience is more limited. If the seizure has stopped, the patient is usually referred to a neurologist. If the patient is actively seizing, the patient is referred to the nearest hospital. The time to treatment gap results in increased morbidity and mortality especially for patients presenting with SE. Unlike developed countries, India lacks a well-organized and responsive 911 type medical emergency system manned by well trained and certified emergency medical technicians (EMTs) and paramedics who can administer life-saving 1st line and 2nd line antiseizure medications such as benzodiazepines (lorazepam, diazepam) and phenytoin or fosphenytoin parenterally en-route to the hospital.

 

Status epilepticus is a neurological emergency. Early effective treatment of SE results in termination of seizure activity and thereby reduction in cerebral hypoxia and damage. Hence every effort should be made to treat SE at the earliest. In India this goal would be best achieved by initiation of treatment of SE at the GP level. Till recently only intravenous benzodiazepine (diazepam or lorazepam) or rectal diazepam was available for the emergent management of seizures and SE. Now drugs which can be rapidly administered via the intranasal or intramuscular routes are also available such as intranasal midazolam and intramuscular fosphenytoin. Neurocritical Care Society guidelines recommend the administration of benzodiazepines via rectal, intramuscular, intranasal or buccal routes if intravenous or oral administration is not feasible. 1Administration via the above routes has been determined to be quick, easy, safe and to achieve high and consistent blood levels of the active compound. 2

 

We feel that antiseizure drugs in these formulations can be easily administered by a GP at the clinic without any special expertise or formal training.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Intranasal midazolam: Currently in Indian market 2 midazolam formulations are available, one is MIDACIP (Cipla Pharmaceuticals) and other is MIDASPRAY (Intas Pharmaceuticals). They are both metered spray preparations. Two strengths of MIDACIP are commercially available: (1.25mg and 0.5mg)

 

Method of administration of MIDACIP nasal spray (Figure 1):

 

 

  1. Shake the bottle gently.
  2. Remove the dust cap.
  3. Hold the bottle with your forefinger and middle finger on either side of the nozzle and your thumb underneath the bottle
  4. If using first time, spray it six times in the air with the nozzle pointing away from the patient until the consistent mist of the drug is delivered, this is called priming, which ensures that correct dose is delivered.
  5. If the patient is in supine position, head is slightly lifted upwards and the device should be placed near the patient’s nose.
  6. Insert the nozzle into patient’s nostril, depress the pump with a firm even stroke. (Patient need not inhale)
  7. Tilt the patient head backward while spraying, this will avoid swallowing of the solution.
  8. Administer one spray at a time in each nostril to continue prescribed dose
  9. Reprime the device for subsequent use if the bottle is not used for more than a day. To reprime spray it two to three times in the air until a fine mist appears. For reusing the device nozzle and dust cap must be washed before storage.

 

 

 

 

Figure 1. Method of administration of intranasal midazolam.

 

Each nasal spray delivers either 1.25mg or 0.5mg of midazolam. Dose is titrated according to individual patient weight and full effective dose should be administered. For adults, dose is 5 mg if weight <50 kg and 10 mg if weight>50 kg. The dose should be equally divided and administered into each nostril. For children the recommended dose of MIDACIP nasal spray is 0.2 mg/kg body weight. The dose should be equally divided and administered into each nostril. Placing half the medication in each nostril reduces the volume while doubling the available surface area for absorption.

 

 

Table 1. Dosing Guidelines of MIDACIP Nasal Spray in children

 

Age (years) Weight (kg) Dose (mg) Metered Doses in Each Nostril
½ – 1 <10 1.25 – 2 1 – 2
1 – 4 10 – 16 2.5 2 – 3
4 – 10 16 – 32 5 4 – 6
>10 > 32 10 10

 

 

 

 

 

 

 

 

Intramuscular midazolam and fosphenytoin: GPs by virtue of their training can administer intramuscular injections with ease. In India intramuscular midazolam (MIDAZ, Abbott Healthcare or FULSED, Ranbaxy Laboratories) injections are widely available and cost effective. Midazolam is given intramuscularly at the dose of 10mg once or 0.2mg/kg once but not exceeding 10mg. Intramuscular fosphenytoin formulations are also available (Fosolin, Zydus Cadila Healthcare or Fosphen, Intas Pharmaceuticals) but more expensive. These preparations are available as ampoules of 150mg (75mg/ml, 2ml). It is our recommendation that the GP administer 2 ampoules of fosphenytoin stat in the clinic prior to transporting the patient to the hospital. Doing so may abort the seizure and possibly terminate the SE.

 

 

Use of the above formulations in the clinic setting by the GP along with established seizure first aid guidelines (Figure 2) has the potential to save many lives and reduce the morbidity from seizures and SE in our country.

 

 

 

 

 

 

 

 

 

 

Figure 2. Seizure first-aid guidelines (Source: Epilepsy Foundation Eastern Pennsylvania, www.epepa.org)

 

References

 

 

  1. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17:3–23.

 

  1. Agarwal SK, Cloyd JC. Development of benzodiazepines for out-of-hospital management of seizure emergencies. Neurol Clin Pract. 2015; 5:80-85.