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It's all about the dose

Published on 15 November 2010
Source: Arthritis Today

Professor David Scott

The use of anti-TNF therapies is constantly being refined and improved. Jane Tadman reports on a new clinical trial that aims to reduce the dosages of these drugs, while maintaining patients’ quality of life.

However effective anti-TNF drugs are in controlling the symptoms of inflammatory arthritis – and their life-changing impact cannot be underestimated – their remarkable success comes at a cost. Between £10,000 and £12,000 per year per patient to be precise. Nor are long-term side-effects known. And no patient wants to be on medication a moment longer than they need to be.

That was the thinking behind a new multi-centre clinical trial about to get underway in hospitals around England led by eminent rheumatologist and current President of the British Society for Rheumatology Professor David Scott.

The trial aims to find out if it is either feasible or desirable – or both – to reduce the doses of anti-TNF given to patients whose disease is currently under control, and even able to come off the medication all together.

If the results are positive it could lead to rheumatoid arthritis (RA) patients being weaned off their expensive drugs –making considerable savings and enabling more people to access them.

Professor Scott, principal investigator of the dose-tapering trial funded by a three-year grant of more than £430,000 from Arthritis Research UK, says weaning people slowly off anti-TNF drugs or even just reducing their dose could have significant benefits.

“No-one wants to be on a drug – however effective – forever, and from the perspective of people with arthritis receiving these drugs, using lower doses should reduce the risk of serious side effects,” says Professor Scott, Professor in Clinical Rheumatology at King’s College Hospital in Denmark Hill, south London.

“So we are asking patients whose disease is well-controlled by anti-TNF therapies to take part in our trial to find out if their dose can be tapered down – without a return of symptoms.

“From the perspective of patients as a whole and society in general, using lower doses to maintain response will make treatment more cost effective, and will enable more people with arthritis to access high cost therapies.”

The Arthritis Research UK clinical trial, involving 99 RA patients in up to 40 hospitals across the UK, could also reduce the risks of serious side-effects by reducing the dose of drugs that people take to keep their disease at bay.

Currently people with severe RA are put on anti-TNF therapy if their disease is not controlled by conventional, cheaper drugs, such as methotrexate and sulfasalazine. Doctors do not know if the maintenance dose required to hold the disease in check should be the same as the initial dose.

The team at King’s College London will show whether it is possible to taper the dose by one-third and two-thirds in patients who had a good response.

“Even if dose-tapering only works in some people, we need to find out.”

“We believe that patients with active RA need relatively high doses of anti-TNF to induce a response, but when they are doing well on these treatments, we think their disease can be kept under control using substantially lower doses,” added Professor Scott. “Some patients may experience a flare-up as a result, but even if dose-tapering only works in some patients we need to find out. If we don’t, it will not be accepted in routine practice.”

Professor David ScottPatients on the trial will be placed in three groups – one group will remain on the standard dose, a second group will have their drugs reduced by a third, and a third group will have their drugs reduced by two-thirds, over a six month period. All patients will stay on their conventional disease-modifying drugs with steroids and anti-inflammatory painkillers as required. Patients on reduced doses whose condition flares up as a result will go back onto their original dose of drug.

Professor Scott said that a positive result should mean that dose-tapering was adopted in hospitals around the country. “Reducing the maintenance dose and thereby increasing cost-effectiveness may persuade regulatory bodies such as NICE to modify existing national guidance so that more people with arthritis can access these effective treatments,” he added.

Lorraine Fanchetti, from Oxted in Surrey, a patient at King’s College Hospital, who has had severe RA for the past 20 years, says she would be very interested to see the results of the dose-tapering trial.

Lorraine is one of the thousands of people in the UK whose life was transformed by the advent of anti-TNF therapy, and would not relish the possibility of being on a reduced dose of the drug that is maintaining her ability to lead a normal life and hold down a demanding job as a central heating designer with British Gas.

She has been on etanercept for the past five years and during that time her quality of life has improved dramatically. “I rarely have to take painkillers and the arthritis is very well controlled, which I put down to Professor Scott’s being quite aggressive in his treatment,” explains Lorraine. “It was very much a softly softly approach to my treatment at first and it wasn’t until the medical team said: ‘right let’s try something completely new’ that things changed.”

Lorraine is so happy with the treatment she has received at King’s College Hospital that she is happy to make the 65-mile round trip to the hospital for her appointments since moving from south London to Surrey.

She appreciates that the dose-tapering trial might be the way forward. “In the long run, I would probably be willing to try having my dose reduced – as long as there was an option to stop as my one concern would be that if I had a flare-up it would have to be managed very quickly,” she says.

“Etanercept is working brilliantly for me right now, but the less medication you are on, the better.”

Rheumatoid arthritis, which affects around 380,000 people in the UK, is caused when the body’s immune system attacks itself, causing inflammation, pain and stiffness in the joints. Other internal organs can also be affected.

There are currently four anti-TNF therapies licensed and approved by the National Institute for Health and Clinical Excellence (NICE) for the treatment of inflammatory forms of arthritis: infliximab (Remicade) etanercept (Enbrel) adalimumab (Humira) and certolizumab-pegol (Cimzia). A fifth, golimumab (Simponi), is licensed but has yet to be approved by NICE.

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