Business India, October 15-28,2001
More than a cure
Rheumatoid arthritis is increasingly being recognised as a crippling disease which affects nearly one crore Indians
Anthrax hogs the headlines and cardiovascular diseases and cancer hog the research dollars, but a crippling disease affecting 60 million people is blissfully neglected or assigned to cold bones and old age. That in short is the story of rheumatoid arthritis. That is why WHO has announced 12 October as World Arthritis Day and will further this decade as the Bone and Joint Decade.
In a series of conferences in Mumbai on 11 and 12 October organised by Aventis Pharma, several well-known clinical experts from the Indian League of Rheumatology Associations did their best to educate the public about this affliction. According to Prof. A.N. Malviya, former professor at AIIMS Delhi and a world-renowned rheumatologist, rheumatoid arthritis (RA) is a highly neglected disease. Even though in a survey done in Ballabgarh semi-urban area near Delhi with a sample set of 39, 000 people, his team found 0.75 per cent afflicted by RA, on a national scale that works out to a massive 75 lakh!
Pain and aching in and around the joints, particularly hands, feet and knees
Swelling of joints
Persistent fatigue and run-down feeling
Muscle weakness and decreased physical activity
Inability to sleep due to painful joints
The disease affects women primarily (female-male ratio is 3: 1) and can occur at all ages, though it is more common post-menopause. Since the 1980s it has also been recognised that besides deforming her beyond repair, RA is serious enough to reduce the life of a patient by 5-8 years.
The cause of RA has not been understood, but it is recognised as one auto-immune diseases, In plain English it means the body's immune system, which is supposed to differentiate between "self" and "non-self' (harmful foreign bodies like bacteria and viruses) gets confused and starts attacking "self" (its own cells). In RA the T- and B-cells (part of body's defences) start attacking the synovium or joint lining (see figure). The synovium gets inflamed and thickened, producing large volumes of sinovial fluid. This causes pain, stiffness, and swelling. When this process is chronic, severe proteins are released, which damage the nearby cartilage and bone, causing erosion. This leads to joint damage, instability, and deformity.
Belatedly its seriousness has come to light. In fact there are just a handful of doctors in India who practice rheumatology exclusively. There are several physicians-cum-rheumatologists and fairly large number of orthopaedics treating the disease. Malviya stresses that educating doctors about the disease is almost as important as educating patients. The most common treatment for RA over the years has been to give the patient painkillers and non-steroidal antiinflammatory drugs like paracetamol, ibuprofen, or the more modern Cox II types, which do not damage the intestines. Malviya prefers to call them "plain killers.” "The disease is surprisingly aggressive. It is not a protracted degenerative disease. If treated within six weeks it can almost surely be arrested. If treated within three months there are good chances, though some damage will have set in. But if delayed any further the damage becomes irreversible," he says. That is why painkillers which just reduce pain and give temporary relief give the patient the impression that everything is okay while irreversible damage is being done beneath the surface.
In the last few decades several drugs have been found to have a very good effect in arresting RA, though they were not initially discovered for that purpose, For example chloroquine, an anti-malarial drug, has been found to have very good effect on RA, in addition to being not expensive. Methotrexate, an anti-cancer drug, has been successfully used against RA and is the most popular treatment today. Malviya, who was one of the pioneers in developing methotrexate therapy, finds it the most effective in combination with other drugs. Sulfasalazine, a drug meant for a bowel disease, has also been found effective against RA.
What these drugs do is affect the rates at which cells divide by interfering in purine metabolism, a necessary step in DNA production - a much-needed raw material for cell division. Now when an autoimmune disease like RA has set in, the body produces too many warriors to fight itself. By reducing cell division, the growth of T- and B-cells is also arrested and hence the beneficiary effect for a RA patient. But the drugs have other side-effects and cannot differentiate between a T-cell and any other cell. Thus, all cell division gets arrested. In fact anti-cancer drugs act in this indiscriminate way and stop the growth of cancerous cells along with healthy cells, leading to severe side-effects in patients undergoing chemotherapy for cancer. One definite precaution to be taken in this therapy is that though the disease affects women more than men, they should not be pregnant since the growth of the foetus also involves intense cell division.
A drug targeted to arrest RA has recently been developed by Aventis Pharma. Leflunomide (trade name Arava) was launched in India on World Arthritis Day. This is a new-generation drug targeted at arresting lymphocyte division by largely interfering in pyrimidine metabolism. It has been found to have an excellent effect on patients in a very short time. However, the drug remains in the system for a long time and does not get expelled through excretion easily. Thus, women planning on conception should inform their doctor of the same so that he can give them additional drugs to flush leflunomide out from the system. which can take a few weeks. So far, leflunomide used to be smuggled into India from Thailand and costs about Rs150-200 per daily dose. However, Aventis is planning to introduce it at about Rs40.
There are also extremely effective biologicals (products of biotechnology) which cost from Rs60.000 a dose to Rs 4.5 lakh. A major concern in this segment is the 56 per cent customs duty that has to be paid and then all the local taxes. Since imports are in small quantities and the government does not really earn much money from this high duty. if these drugs are made duty-free then thousands of RA patients will get some relief from pain to their pockets as well!
Interestingly, as one of those wonders of nature, though RA patients cannot take any of the above-mentioned disease-modifying treatments during pregnancy, the body itself arrests RA and there is a temporary remission!
"The main problem today is educating the patients and the general population," says Dr K.M. Mahindranath, a renowned rheumatologist from Bangalore and president-elect of the Indian Rheumatology Association. "Since it mostly affects women, the initial symptoms of prolonged morning stiffness are taken as a sign of laziness by family members. Then, as the patient loses control over her fingers and starts dropping things she will be called clumsy and when she becomes sloppy and cannot even dress herself properly she stops going out and becomes a recluse. This in turn leads to depression, which worsens the problem. What is needed is proper counselling and encouragement to engage in appropriate physical therapy and other exercises. in addition to drugs." he adds. He welcomes Aventis's initiative In this regard through its newly launched "joint Effort" - where Aventis facilitates communication between the physician and patient using its own network of 200 medical representatives and 10 trained counsellors.
"We have exclusive marketing rights for Arava in Europe and North America, but owing to the IPR regime in India we do not enjoy any protection here. Therefore, it is to be expected that this drug, which in a short period of two years has reached sales of $250 million will be copied by some Indian companies and introduced in the Indian market. But there are two issues. Firstly, the drug has to be produced in extremely controlled conditions where there are no women workers and where no other drug is produced. If the authorities here insist on these manufacturing practices, I doubt anybody will qualify, considering that today only one factory in France supplies to the whole world and a new factory only to serve the small Indian market does not make economic sense. Secondly, RA therapy is more than just drugs. It means counseling, communication, and actually building a long-term relationship with the patient of which our Joint Effort will be a key component. I seriously doubt if any other company will invest in this." says Aventis CEO Ramesh Subramaniam.
But there are researchers who are trying to find out in detail how herbal drug therapies work using tools of modern medicine. C.N. Qazi, director of the Jammu Regional Research Laboratory of CSIR, and his predecessor S.S. Handa are two of this breed. Handa started work on boswellic acid extracted from the gum produced by the tree Boswellia sarata found in the forests of Madhya Pradesh. The beneficial effects of these guguls and gums for arthritis are cited in ayurveda. Handa studied the anti-inflammatory character of boswallic acids extensively over the last two decades. The standardised boswellian extract is being marketed by Gufic Laboratories under the brand name Salaki.
Qazi has picked up where Handa left off. He studied the other fractions in the extract and found those that are not just anti-inflammatory but actually immuno-modulatory in nature. The method of extraction, preparation, and use of these compounds have been patented by CSIR in Europe and the US, and animal trials too have been conducted with no toxic effect. Human trials are still to be done, but since herbal medicine does not require human trials, CSIR is negotiating with some companies to market these Immunomodulatory extracts, which have been effective in the arrest of arthritis. The research has generated a lot of interest internationally and this CSIR laboratory is getting a lot of snail mail and e-mail.
Tuesday, August 7, 2007
Business India, October 15-28,2001