EDITORIAL - Promoting science over serendipity in prescribing anti-TNF therapy

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Rheumatology Advance Access originally published online on April 29, 2009

Rheumatology 2009 48(8):865-866; doi:10.1093/rheumatology/kep095

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Editorial

Promoting science over serendipity in prescribing anti-TNF therapy

Meng M. Chee1, Nicola Alcorn1, Paterson2 and Rajan Madhok1

1Centre for Rheumatic Diseases and 2Department of Clinical

Pharmacology and Diabetes, Glasgow Royal Infirmary, Glasgow, UK

In the past, rheumatologists may have been perceived by some

specialist colleagues as purveyors of toxic drugs for only modest

benefits. Some physicians may have had the opinion that we treated

complex conditions which were poorly understood with potent drugs

whose mechanism of action was largely unknown. The withdrawal of

several anti-rheumatic drugs over the years and the ensuing publicity

may have perpetuated this idea; for example, benoxaprofen was

withdrawn in 1982 due to hepatotoxicity and more recently some

COX-2-specific inhibitors were also withdrawn due to an increased risk

of ischaemic events. As rheumatologists now adopt management

strategies to prevent disability rather than just managing it,

perceptions of the risk–benefit relationship of DMARDs too may be

changing. Many of the original DMARDs arose out of serendipity rather

than science; as a direct result of an improved understanding of the

pathophysiology of rheumatic conditions we now have targeted

biological therapies, the first of which was anti-TNF- therapy.

Anti-TNF- drugs were developed to target a specific inflammatory

cytokine known to be vital in inflammation. This novel treatment has

revolutionized the management of RA and is increasingly being used in

the treatment of other autoimmune rheumatic diseases. While it was

initially used with caution a decade ago, it is now widely used in

clinical practice and has transformed the lives of many RA patients,

dispelling visions of chronic disability and giving hope of an

improved quality of life to many. Double-blind randomized controlled

trials—the primary instruments for measuring treatment effects and

defining common adverse events in a select group of patients—not only

proved the significant benefit of anti-TNF- therapy but also

highlighted the risks of infection and tumours [1]. Patients in

routine clinical practice, however, often have comorbidities and will

be on co-existing therapies, which not only influence efficacy but may

reveal new side-effects. As patients will also invariably be on the

drugs indefinitely, the potential long-term effects continue to give

cause for concern. A decade on, less common but equally important

adverse events associated with anti-TNF- treatment are becoming

apparent; for example, anti-TNF- treatment in some may not only induce

autoantibodies but in a minority may also lead to clinical expression

of autoimmune diseases [2]. Some of these adverse events may also

provide insights into the pathogenesis of other poorly understood

disorders.

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Read the full editorial here:

http://rheumatology.oxfordjournals.org/cgi/content/full/48/8/865?etoc

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