Quantum leap for treatment

MEDICAL MATTERS: It is not often that a major breakthrough in the treatment of a particular disease is made. Most medical advances happen in small finite steps which cumulatively improve treatment and quality of life for patients.

However, in the case of rheumatoid arthritis (RA), it now looks as if just such a quantum leap has been achieved following the approval of a new range of drugs with the ability to stop the disease in its tracks.

RA affects about 35,000 people in the Republic. Some 75 per cent of these will experience a relatively slow onset of the disease; 20 per cent will have moderately progressive RA with one in 20 having an illness that is rapidly debilitating. It is estimated that up to 30 per cent of patients are unable to work within two years of the condition's onset.

The arthritic disease causes irreversible damage to certain joints in the body. Permanent damage to the cartilage and the bone surrounding the affected joint occurs quite early on in RA. Essentially what is happening is that the body's immune system - which normally counteracts threats from outside - turns on itself and begins to attack the joints.

RA usually starts between the ages of 40 and 60 and affects women three times more often than men. Until recently RA was seen as a somewhat "hopeless" disease in that people would end up with chronic pain and severe deformity no matter what you tried to do for them. Treatment was largely confined to combating the pain and the inflammation.

Within the past five years, however, it has been possible to say to people with RA that there is real hope of actually modifying the disease process itself, thereby preventing the life-long deformities and disability usually associated with the condition.

New "biological agents" - so-called because they are derived from antibodies - are now available and are aimed at specific steps in the rheumatoid process so that the inflammation is literally stopped in its tracks. One class of the new agent targets a substance called tumour necrosis factor (TNF). This protein plays a key role in the disease process. It is also known to promote bone breakdown around joints as well as reducing the manufacture of an essential component in cartilage. A second class of drug blocks the receptor for a substance for Interleukin 1 (IL-1) which has a similar function.

There are now three anti-TNF drugs available in Ireland. Adalimumab is the most recently introduced, joining Etanercept and Infliximab.

While all acting in the same way, the three drugs vary considerably in how they are administered. Infliximab is given by intravenous infusion every four to six weeks. Etanercept is taken twice weekly by injection into subcutaneous tissue. The latest agent, Adalimumab, which has the potential advantage of being derived from human antibodies, is administered by the patient every fortnight by means of a subcutaneous injection. The new agents are not cheap; it costs between 800 and €1,300 for a month's treatment.

The new biological agents produce dramatic improvement in symptoms for about 70 per cent of people treated with them. Consultant rheumatologists, who are the only ones licensed to prescribe the new drugs here, tell of dramatic and life changing results. One man who was unable to work has returned to a relatively demanding physical job. Another has reportedly been able to take up rugby again. A mother of three who used to have to plan how to get up out of her chair based on which joint was particularly sore, reached the living room door one day before realising that she had done it without having to think about getting there.

However, and it is a big however, the anti-TNF agents can over-suppress the immune system leading to the risk of serious infection. The big fear is that of precipitating TB with about one in 10 of those treated at risk. Patients with active TB or other severe infections cannot take the new agents and there is also a risk of reactivating a latent form of tuberculosis. Pre-treatment testing for TB is mandatory and patients must be monitored closely during and after the new drug therapy.

The new agents are now being assessed to see if they can be used to successfully treat other arthritic conditions such as psoriatic arthritis and ankylosing spondylitis. But already they are being hailed as the biggest breakthrough in the treatment of rheumatoid arthritis in decades. Dr Conor Mc Carthy, consultant rheumatologist at the Mater Hospital in Dublin, compares the drugs to the discovery of steroids for RA treatment 40 years ago and while he doesn't anticipate that the biological agents will have the unacceptable toxicity subsequently associated with long-term steroid use, he says we must be cautious in their use.

But perhaps the biggest difficulty will be enabling patients to access the new treatments. Because they cannot be prescribed by GPs, patients must be seen quickly by a specialist. Writing about the need for early referral in a recent edition of Clinical Forum, Dr Niall Maguire, a GP in Navan, said: "However, this [early referral\] is easier said than done and it is a matter of considerable concern for GPs working in the several regions which are underserved by rheumatologists at present."

• Muiris Houston is pleased to hear from readers at mhouston@irish-times.ie but regrets he cannot answer individual queries