Biologic drugs for the treatment of rheumatoid arthritis (RA) are made from proteins. They work by specifically blocking the activity of chemicals or cells involved in the inflammation that gives rise to joint swelling and other symptoms.
In the 1980s it was discovered that the inflamed joints contain many different chemicals that cause inflammation. Cytokines are an example of such an agent. They are small proteins whose job is to send chemical messages from one cell to another – some switch off inflammation while others are potent at causing it. The cytokine tumour necrosis factor (TNF) has been shown to be responsible for regulating a number of other important pro-inflammatory cytokines. The TNF acts like a chemical ‘ringleader’ encouraging other cytokines to cause pain, swelling and stiffness. Clinical trials of biologic therapies that inhibit the activity of TNF (for example adalimumab and etanercept) showed that most patients, although not all, improved with this treatment.
Standard DMARDs (such as methotrexate, salazopyrine, hydroxychloroquine and leflunomide) are non-specifically acting drugs that have a variety of effects on different inflammation processes. Biologics, in contrast, are ‘designer drugs’ that specifically act on the important inflammation pathways.
Some of the newer biologic treatments target other areas of the immune system that are involved in the processes of inflammation. These include other cytokines such as IL-6 and cells such as B and T lymphocytes.
Unfortunately biologics do not work for everyone. Some people have to stop taking them because of side effects and others, because they experience no benefit. There is currently no reliable way to work out in advance who will benefit; it’s a question of trying it out and waiting to see if it works. It is usually evident within three to four months if they are beneficial. Anti-TNFs often work quite rapidly and many patients begin to feel better within a couple of weeks after the first treatment. Many people often find that they have more energy and less fatigue.
As the anti-TNF is a protein, it will be rapidly digested in the stomach, and therefore these drugs need to be given by a self-administered subcutaneous (under the skin) injection, or in the hospital by an intravenous (into a vein) infusion.
There are strict eligibility criteria which need to be fulfilled in order to qualify to receive the biologics. You may be eligible if: you have failed to respond to treatment with at least two standard disease modifying drugs (DMARDs), one of which is usually methotrexate AND your rheumatoid arthritis disease activity score (DAS 28) is measured as 5.1 or over on two occasions.
The most common side effects of biologics are related to minor reactions at the site of injection. Very rarely, there may be an increased risk of infection which includes a reactivation of TB.
Biologic therapy is an exciting, effective (and expensive) treatment for rheumatoid arthritis and other autoimmune diseases.
Adapted from Biologics, the story so far NRAS, Sept 2013