The story so far: Earlier this week, The Lancet published the results of a study that proposed to repurpose an existing drug to treat rheumatoid arthritis as prophylaxis, to prevent disease. Can doctors prevent the onset of rheumatic arthritis in people (with indicative biomarkers) who have not yet developed the condition? The results of the study showed that “rheumatoid arthritis prevention trials are feasible and targeting the adaptive immunity of such individuals at an early stage, can prevent the onset of rheumatoid arthritis.”
What is rheumatoid arthritis?
It is a chronic, autoimmune condition that mostly affects the joints. Scientists have not yet understood why an autoimmune condition occurs, allowing the immune system that protects the body, to attack itself. A patient experiences pain, swelling of joints and loss of function and mobility as a result of stiffness. As can be expected, this is likely to significantly lower a patient’s quality of life. As per the National Institute of Arthritis and Musculoskeletal and Skin Diseases, of the National Institutes of Health, U.S., rheumatoid arthritis affects the lining of the joints, and damages the tissue that covers the ends of the bones in a joint. It often occurs in a symmetrical pattern, meaning that if one knee or hand has the condition, the other hand or knee is also often affected. Fatigue, occasional fevers, and a loss of appetite are to be expected, and there is a possibility that it may cause medical problems outside of the joints including in the heart, lungs, blood nerves, eyes and skin.
What did the study attempt to do?
Andrew P. Cope et al explain in the paper that the idea was to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with an existing drug, Abatacept, to treat rheumatoid arthritis.
The drug is a ‘co-stimulation modulator’ acting as a signalling pathway to start the appropriate immune response.
At the core of their experiment is the understanding that individuals at high risk for rheumatoid arthritis can be identified years before they actually develop the disease, even as early as decades earlier, by detecting autoantibodies associated with rheumatoid arthritis known as Anticitrullinated Peptide antibodies (ACPAs), in the blood.
Although the presence of autoantibodies might precede disease onset by a decade or more, the combination of ACPA with symptoms, and evidence of subclinical synovitis (inflammation of the lining of the joint) by imaging, has increased the predictive power of identifying individuals who are most likely to progress to rheumatoid arthritis within two years. These features have provided a framework for evaluating therapeutic strategies that could delay or prevent disease onset, the authors say.
The results show that rheumatoid arthritis prevention trials are feasible and targeting adaptive immunity at an early stage, with Abatacept, an existing drug for RA, before clinically apparent arthritis is manifest, can prevent the onset of rheumatoid arthritis. The drug of choice is Abatacept, a biological disease-modifying anti-rheumatic drug which works by selectively modulating signals to spur T-cell activation, or begin the body’s immune response.
What’s the Indian scenario with regard to rheumatoid arthritis treatment?
Rohini Handa, eminent rheumatologist at Apollo Indraprastha Hospitals says: “This is a story that has been going on for years — how do we delay the progression of rheumatoid arthritis?” Abatacept, a drug that comes under the classification ‘biologicals’, he points out, is no longer available in India; it was withdrawn after it did not sell well in the Indian market. But in the last five years, there have been six drugs to treat rheumatoid arthritis. At the moment, worldwide, 10 biologicals are available, and six of them in India. About three years ago, a group of drugs called JAK inhibitors came off patent, and one of those drugs — tofacitinib — is available at ₹900 for a month’s supply. It is also an oral drug, as against biologicals that might be intravenous, or a subcutaneous injection, depending on which part of the world one is in, he says. “No biological can compete with this.”
Is early prevention of the disease significant?
So far treatment hinges on starting early, Dr. Handa explains. “If someone has a family history, such prevention has intuitive appeal. Autoantibodies come up years before the symptoms appear. If you are able to switch off the autoimmune system going errant, then that definitely has great appeal.” However, there are some grey areas in using such preventive methods. “To use drugs for something that will likely happen 20 years from now, you will have to convince someone with a blood abnormality and no physical abnormality to start treatment. What is the end point for this, then? When do we cease treatment?” Dr. Handa asks. The study confirms this apprehension.
Also read | ‘Rheumatoid arthritis also affects other parts of body’
Pre-disease treatment with Abatacept reduces progression to clinically-apparent arthritis during the 12-month treatment phase, and up to 24 months after stopping treatment. However, by 24 months, the parameters of those who received the drug were similar to those with the placebo group; it was similar between groups, indicating that treatment is not sustained. “We employ a common-sense approach — we tell all patients that smoking is a strong risk factor, and urge them to refrain from smoking, to exercise and eat healthy. These can be implemented on a mass scale, and we should ensure this message gets through,” Dr. Handa says.
- Rheumatoid arthritisisa chronic, autoimmune condition that mostly affects the joints. Scientists have not yet understood why an autoimmune condition occurs, allowing the immune system that protects the body, to attack itself.
- The Lancet published the results of a study that proposed to repurpose an existing drug to treat rheumatoid arthritis as prophylaxis, to prevent disease.
- Andrew P. Cope et al explain in the paper that the idea was to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with an existing drug, Abatacept, to treat rheumatoid arthritis.
Published - February 18, 2024 02:28 am IST
