Pharmaceutical review



I would like to point out some inaccuracies that appeared in the recent pharmaceutical review article [1] which reported the results from the National Institutes of Health, Medical Treatment of Prostatic Symptoms (MTOPS) study. The full MTOPS data has yet to be published, but given the available data presented at last year's annual meeting of the AUA, the opening paragraph of the review is clearly incorrect. It states that the combination of a 5α-reductase inhibitor (finasteride) and an α-adrenoceptor antagonist (doxazosin) has advantages over either agent alone in preventing the clinical consequences of BPH (acute urinary retention, AUR, and the need for surgery). Apart from this statement being inaccurate (see below), the primary endpoint of MTOPS considered more than AUR and the need for surgery. It was composite, defining disease progression as the occurrence of an increase of ≥ 4 points in the AUA symptom score, AUR, urinary incontinence, recurrent UTIs and renal insufficiency. Not unsurprisingly, symptom deterioration accounted for the significant proportion of this headline rate. Given this definition of BPH progression, combined therapy was indeed associated with a risk reduction of 67%, while monotherapy with doxazosin or finasteride showed risk reductions of 39% and 34%, respectively.

The clinical consequences mentioned by the author (AUR and the need for surgery) were reported independently and the results are contrary to the author's comments. MTOPS showed that at 5.5 years finasteride significantly reduced the incidence of AUR compared with placebo (a risk reduction of 67%). Furthermore, there was no significant difference in risk reduction between the combination (79%) and finasteride monotherapy. However, this was not the case for doxazosin, with the study reporting that the risk reduction in the incidence of AUR for doxazosin alone was not significantly different from placebo. Similarly, only the combination and finasteride arms significantly reduced the incidence of invasive therapy for BPH (a risk reduction of 69% and 64% vs placebo, respectively). Again, the difference in risk reduction was not clinically significant between the finasteride and combination groups. As with the incidence of AUR, there was no significant benefit with doxazosin in the incidence of surgery over placebo after 5.5 years.

We look forward to full publication of the MTOPS data to better understand the potential role of combined therapy in managing BPH. On present evidence, combined therapy is valuable in reducing symptoms but does not appear to offer significant benefit over finasteride monotherapy in reducing AUR and the need for surgery.


On the basis of the data that are in the public domain from the MTOPS study, Mr O’Reilly is absolutely correct that there is no evidence that the combination is superior to either agent alone for AUR and surgery. Hopefully, we will soon see official publication of more data of the type that was recently presented at the EAU by Professor Roehrborn; this will enable us to decide more appropriately on the relative clinical merits of monotherapy versus combination.