Smart drugs bring hope to arthritis sufferers

Smart drugs bring hope to arthritis sufferers
Published: 13 June 2007
Independent UK

Three cutting-edge "smart" drugs have ushered in a new era of treatment for sufferers of rheumatoid arthritis, scientists said today.
Each consists of molecules that target different parts of the immune system.

Two drugs, MabThera and Orencia, are licensed in the UK, although the latter was only launched this month. The third, tocilizumab, is still undergoing trials.

Researchers who analysed trial data on the drugs said all three slowed progression of the disease and reduced its symptoms. All achieved the best results when used in combination with the standard treatment methotrexate.

The scientists, led by Professor Josef Smolen, from the Medical University of Vienna in Austria, wrote in an online edition of The Lancet medical journal: "The emerging agents show that a new era has started in the treatment of rheumatoid arthritis."

Rheumatoid arthritis (RA) is a painful and sometimes crippling auto-immune disease which affects an estimated 400,000 people in the UK, 4,000 of them seriously. It occurs when the immune system attacks the joints, causing swelling and damage of cartilage and bone.

Traditional treatments for RA include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid steroids, and disease-modifying antirheumatic drugs (DMARDs). Methotrexate, the most widely used DMARD, is a cornerstone of most treatment regimens.

All these treatments have limited effectiveness, and even responses to newer biological agents such as tumour necrosis factor (TNF) inhibitors may be restricted, said the researchers. Further advances and more treatment choices were therefore needed.

MabThera, the brand name of the drug rituximab, is also used to treat lymphoma cancers.

Like tocilizumab it is a monoclonal antibody (mab), an artificial version of the immune system agents that stick to invading cells and cause their destruction.

MabThera targets B-cells, white blood cells which themselves generate antibodies. In RA, the B-cells are wrongly programmed to launch antibodies against the patient's own joints.

Trials of MabThera showed that the drug reduced RA symptoms by over 50% for more than a third of patients.

Orencia (abatacept) works in a different way, by interfering with the activation of T-cells, another type of white immune system blood cell. A trial combining Orencia with normal methotrexate treatment also found a 50% reduction of symptoms in some 40% of patients.

Tocilizumab hones in on interleukin-6, a signalling molecule known to activate many cell populations. Combining the drug with methotrexate had a similar impact on symptoms as Orencia and MabThera.

Side effects varied, with patients reporting higher rates of serious infection when being treated with MabThera or Orencia. Some patients taking tocilizumab experienced headaches, skin eruptions, fevers and increased cholesterol levels.

The authors wrote: "The many patients who obtain insufficient responses to established and novel treatments indicate the need to search for further therapies and treatment principles to increase response rates and to achieve high frequencies of remission or even cure in rheumatoid arthritis. The prospects are here."

The National Institute for Health and Clinical Excellence, (Nice), which issues guidelines on which medicines should be available on the NHS, is looking at the use of MabThera and Orencia for treating RA.