This was released at the BSR Annual Meeting in April 2007 and is accessible through the BSR website.
There have been major problems for some departments which have found that they are constrained by the adoption of a fixed new:follow-up ratio. This is a performance indicator that suddenly emerged from the Department of Health about 4 years ago although its validity in chronic disease specialist management is dubious. Should you require information on how to deal with the issue, email Dr Bamji
29th July 2010
Biologic agents and the risk of cancer
Alan Silman has kindly provided the analysis below on the recent JAMA paper suggesting an increased risk of malignancy with some biologic agents.
Whereas meta-analyses of randomised clinical trials (RCT's) are frequently used to derive robust estimates of efficacy, the data gathered in trials on potential long term hazards is not routinely subjected to a similar pooled analysis. Randomised clinical trials, such as those of TNF monoclonal antibodies in rheumatoid arthritis (RA) are too small and of too short duration to provide useful data of rare but serious long term hazards. In addition RCT’s are typically conducted on lower risk patients, ie those with significant current or recent co-morbidity are excluded.
In an attempt to overcome the small number problem from using RCT data, Bongartz et al have conducted a meta-analysis of the incidence of cancer occurring in the different treatment arms of the published anti-TNF monoclonal trials. Their results suggest a threefold increased risk of malignancy in anti-TNF treated patients compared to those in the standard treatment arms of the trials included; with the risk concentrated in those exposed to high doses of the agents. These data therefore raise concerns about the safety of anti-TNF monoclonal antibody therapy, especially when used at high doses.
There are however a number of areas of caution required. Firstly they did not include etanercept, which is the most popular used anti-TNF agent in the UK. The authors argue from biological principles that etanercept may not be expected to have the same risk. Secondly the high doses referred to were based on an infliximab dose of ≥ 6mg/kg body weight per 8 weeks, a dose higher than the standard UK regime of 3mg/kg. Thirdly in the trials considered some of the cancers were ascertained after the trial following notification to the FDA, it is not clear whether this would have been more likely for subjects treated with anti-TNF. Fourthly, many of the cancers were basal cell skin tumours which have a benign prognosis. There were also a surprising number of malignancies diagnosed within a short period of time after the trials commenced suggesting that their onset may have antedated the therapy. Excluding these very early malignancies and the benign skin cancers did not however eliminate the increased risk. Fifthly the study did not consider rates of events (per 1000 person years for example) because the individual duration data was not available to them. The drop out rate was higher in the placebo arm which might have exaggerated the risk in the active arms of the trails considered. Finally, and of possible greater importance, the malignancy rate in the control arms was unexpectedly low. Amongst 1512 control subjects, followed for what would appear to be a year on average, there was only 1 malignancy, excluding the two basal cell carcinomas. In a typical RA population, or indeed a general population sample of this age group, one might expect an incidence of around 8/1000 per year.
For all the reasons therefore the results from Bongartz et al should be treated with caution at this stage. An informed estimate of any increased risk of cancer will need to await data from the carefully conducted prospective studies being undertaken in several countries.
Updated 8th August 2006
For more information about the Register visit the Register website
Changes in the NHS have the potential to affect rheumatology departments across the UK. Most acutely, the sudden emergence of deficits in secondary care has led to threats to staffing and prescribing. We have heard that consultants may not be replaced and that specialist nurse posts are being disestablished. Problems of prescribing of biologic agents remain, as outlined in a recent press release from ARMA and the BSR. There has been pressure on departments to reduce the number of follow-up patients seen
The White Paper "Our Health; Our Care; Our Say" and the musculoskeletal framework document are underpinned by the assumption that it is necessary to move services from secondary to primary care. In the case of the latter there are many things that are good - but the proposals for interface management (Clinical Assessment and Treatment Services, or CATS) are not as we expected. All rheumatologists should examine this part very carefully, else you will find that CATS are being set up without your input, which will be potentially disastrous.
Some specialists may be expert at riding the waves, while some, we know, are less so. We believe that the most important part of any case to protect or preserve services is to show that they are cost-effective (and even that alternatives may be less cost-effective).
Locally we have produced several papers directed at specific proposals that might have adversely affected our department and their use has been successful in convincing others of our case. If you would like to have a copy of any of those listed below for which a direct link is not provided, then please email.
Rheumatology Specialist Nurse: business case (February 2006)
Secretarial services review (May 2006)
Reducing rheumatology follow-ups (August 2006 - updated March 2010)
Rheumatology Service Review (October 2006)
Dr Foster contains other comparative data. You can get access to a full range of data by setting up an account; ask your hospital managers how to do this.
If you have produced any useful documents, or wish to suggest links, please email