Home > meeting report > Meeting report (part 2): Biological treatment of rheumatic diseases with special focus on T cell modulation

Meeting report (part 2): Biological treatment of rheumatic diseases with special focus on T cell modulation

Meeting report (part 2): Biological treatment of rheumatic diseases with special focus on T cell modulation

The meeting at Karolinska Institute Center for Molecular Medicine continued with a very interesting state-of-the-art lecture on safety of biologic treatment in rheumatic diseases, given by Johan Askling, associate professor rheumatology (photo). His lecture was structured in three sections: first some facts about cancer occurrence in rheumatoid arthritis, then a part adressing cancer occurrence related to treatment strategeis of rheumatoid artritis, and finally some clinical considerations to conclude with.

As far as the occurrece of malignancies in rheumatoid arthritis, irrespective of teratment concerns it has become clear that at the time of RA diagnosis patients are no ore likely to have any form of malignancy as compared to the general population. The overall burden of cancer in rheumatoid arthritis patients however is marginally elevated (10-15%). Whereas one-third of the general population will eventually develop some form of malignancy in their life, in rheumatoid arthritis there appears an increased risk for developing lymphoma, lung malignancies and non-melonma skin cancer, whereas these patients actually seem to have a reduced risk of developing some other forms of malignancy such as colorectal or breast carcinoma. In conclusion there appear to be site specific increased as well as reduced risk for developing malignancy in rheumatoid arthritis patients.

Reports on risk of developing malignancies from several treatment strategies in rheumatoid arthritis have been published so far. Whereas methtrexate and azathioprin treatment may slightly increase the risk of developing lymphoproliferative disease and sulphasalazin as well as NSAIDs might to some extent rather prevent development of colorectal cancer, these associations seem no major contributing factors but on the other hand methotrexate and azathioprin can also not be ecluded as risk factors. Whether treatment strategies using TNF-alpha blocking agents increase the risk for developing malignancies or not is part of an ongoing debate. Nevertheless, since this debate has been going on already for several years, and an icreasing number of studies, meta-analysis and data from registries has become available, the picture is getting more clear and allows for better base clinical considerations and decision making by physicians in cooperation with the patient. A meta-analysis paper evaluating data of 74 clinical trials with anti-TNF-alpha treatment concluded that there was almost no increased risk for developing cancer under this treatment regimen. (Citation weblink: Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data)This conclusion is justified for all types of cancer except for non-melonoma skin malignancies for which an increased risk to develop within months of anti-TNF-alpha treatment was shown. However the studied trial population is not fully comparable with the current population that is being treated with TNF-alpha-blocking agents. A more recent Canadian meta-analysis of 6 trials that included only early rheumatoid artrhritis patients however did also not indicate an increased risk. (Citation weblink: “Tumor necrosis factor therapy and the risk of serious infection and malignancy in patients with early rheumatoid arthritis: a meta-analysis of randomized controlled trials.“) Data from the Swedsch Registry did not show an elevated risk for for developing cancer within 5 years of anti-TNF-alpha treatment. At the ACR 2011 meeting similar data were presented from a survey of the British Rheumatology Society in which no differences in cancer occurrence were found for DMARD therapy as compared to DMARD therapy combined with anti-TNF treatment.

Both for these metaanalyses and for the registry data conclusions refer to overall burden of cancer, however what about site specific cancer riks? Both from USA incidence data as from Swedish Registry incidence data anti-TNF-alpha treatment appears to be linked to melanoma development, but not for non-melonma skin cancer. There is a 1.6 to 2.0 relative risk for developing melanoma when treated with anti-TNF-alpha. Translated into daily clinical practice decision making one might prefer to talk about this in numbers to threat terminology for the patient to have a better idea of the actual risk, since relative risks can be statistical terms that may cause some interpretations problems for patients. So, one could also argue that statistically 1 out of every 4,000 patients treated with TNF-alpha blocking agents will develop melanoma. It’s up to the doctor and the patient to consider this -as weighing any other- risk in deciding to start treatment or not. Here one might strive for developing “benchmark risks” which can be defined in the same way (how many in a thousand treated patients are expected to develop…). One can then compare these risks to other (sometiems more familiar) risks as e.g. risk for being involved in a fatal traffic accident (risks as compraed to other risks).
It is advcated to avoid use of TNF-alpha-blocking agents in patients with a history of melanoma and be cautious in case of a history of lymphoma. For lymphoma, a more recent report (Citation weblink: Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis) did not find a significantly nicreased risk upon treatment with anti-TNF. As far as cancer recurrece upon starting anti-TNF therapy concerns few data are currently available from a German and British study. However these reports include rather small number of patients and do not allow for conclusions supported by strong evidence yet. As far as non-TNF-alpha-blocking treatment of rheumatoid arthritis concerns it is also a matter of “too early to tell” at this moment because apart from trial data there are not much observational data available yet. So in general the risk of developing cancer in rheumatoid arthritis is quite similar as for the general population and one of the major advices therefore remains to quit smoking.

Before it was lunchtime on day 1 of the meeting Iva Gunnarsson, also associate professor rheumatology, continued with a lecture on SLE and biological treatments. This will be summarised in part 3 of this emeting report (to follow).

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