The literature review cited in the ACP guideline noted that multiple cohort studies reported that patients who did not achieve a serum urate level
Moreover, the ACP doubled down, stating that “even if urate-lowering therapy does reduce gout flares, these studies do not help us understand the tradeoff between the magnitude of benefit and the harms and costs incurred by treatment and monitoring.” The harms and costs of monitoring urate levels are not described, but the potential harms and costs of urate lowering drugs are noted and, for the most part, none of those cited are dose dependent or related to hypouricemia.
On the one hand, the ACP guideline discusses the use of urate-lowering therapies and the relative cost and efficacy of the various drugs used. But if the ACP does not believe that the reduction in the frequency of gout attacks is related to the institution of urate-lowering therapy and reduction of serum urate to a target level, then why would one even begin urate-lowering therapy in the first place? Indeed, the guideline notes that “… the evidence is graded as moderate quality that longer-term urate-lowering therapy (>1 year) reduces gout flares. We consider the magnitude of this reduction uncertain.”
Thus, there is both cost and potential for harm in the use of urate-lowering therapy and little potential benefit, according to the ACP’s analysis. Moreover, as the guideline notes, institution of urate-lowering therapy actually increases the frequency of acute gout flares in the short term, and the guideline recommends concomitant prophylaxis with another drug for eight weeks after instituting urate-lowering therapy, which increases the cost and potential for harm even more. Additionally, some of the placebo-controlled studies cited would suggest that discontinuation of concomitant colchicine at eight weeks leads to a marked increase in acute flares that seemed to recede after six months.
My Questions
So why would anybody start a therapy of uncertain benefit that is well documented (via randomized controlled trials) to increase patient’s symptoms (increased frequency of gout flares)? And how did we get to this point in coming up with our guidelines?
Clearly, randomized, placebo-controlled trials are the gold standard in evaluating therapies, and the evidence provided by these studies is given the greatest weight in developing clinical guidelines. But sometimes other evidence can be quite compelling; nobody has ever tested penicillin against placebo for the treatment of pneumococcal pneumonia, an infection that used to carry a 35% mortality rate. Indeed, the ethics of conducting a placebo-controlled trial of penicillin in the treatment of pneumococcal pneumonia are dicey at best.
