Longwoods Blog

Monday, August 22, 2011

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As readers of these pages are well aware, there is currently only one prescription drug (orlistat) for the long-term management of obesity and recent applications for new anti-obesity drugs have run into considerable obstacles with licensing agencies, not least the US Food and Drug Administration.

Thus, despite meeting criteria for efficacy, recent applications for new anti-obesity drugs were rejected due to safety concerns, the argument being that the expected widespread use of these drugs warrants higher standards of safety than for drugs in other therapeutic areas.

This may well be true, if anti-obesity drugs are indeed to be made freely available (even on prescription) and are to be used without careful consideration of the risk/benefit ratio.

As discussed previously in the context of bariatric surgery, the risk side of this equation is not limited to the ‘risk’ associated with treatment but must also include the ‘risk’ associated with not treating the condition.

As our recent papers on the Edmonton Obesity Staging System (EOSS) clearly show, the ‘risk’ associated with obesity varies considerably – from virtually no risk for patients with EOSS 0 to very significant and immediate risk for patients with EOSS 3.

So, while even the smallest treatment-related risk may be unacceptable for treating obesity in a patient with EOSS 0, a higher level of risk would be certainly be acceptable with higher EOSS stages – or in other words – the greater the risk of not treating, the greater the acceptable risk for a potentially beneficially treatment (which, for e.g., is why cancer warrants the considerable treatment risks of chemotherapy).

Of course, this would mean that rather than having to prove the safety and efficacy of anti-obesity drugs in anyone with a BMI over 30, it may be enough to show that these drugs are effective and safe enough to warrant their use in people with higher EOSS stages (2/3) – the greater the risk of the target population, the greater the acceptable risk of treatment.

This should not be difficult. We know that many of the conditions that patients with EOSS 2/3 present with can be ameliorated even with rather modest weight loss. For these patients, the 5-10% sustainable reductions in body weight that can be achieved with anti-obesity drugs, can have very significant health benefits, which would easily outweigh and justify a reasonable risk of adverse effects – a risk that may be unacceptable in patients presenting with EOSS 0/1 obesity.

This, of course means rewriting some of the approval criteria and guidelines for anti-obesity drugs, but also requires redesigning pharmacological trials to focus on the high-risk EOSS 2/3 patients rather than on the low-risk EOSS 0/1 patients.

I certainly look forward to following how this discussion evolves and wether or not we can indeed find a way out of the current impasse of anti-obesity drug development and approval.

AMS
Toronto, Ontario

Padwal RS, Pajewski NM, Allison DB, & Sharma AM (2011). Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne PMID: 21844111

Kuk JL, Ardern CI, Church TS, Sharma AM, Padwal R, Sui X, & Blair SN (2011). Edmonton Obesity Staging System: association with weight history and mortality risk. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme PMID: 21838602

This entry was posted on Monday, August 22nd, 2011 at 10:59 pm and is filed under Longwoods Online.