BERKELEY, CA (UroToday.com) -
Mycophenolate Mofetil NIDDK Trial Fails to Demonstrate Efficacy
If the etiology of IC/BPS is in part due to an induced autoimmune/inflammatory disorder, immunosuppressant therapy is a reasonable consideration for a treatment trial. Two open label trials from Finland showed that cyclosporine produced short-term and long-term pain resolution, decreased frequency, and increased voided volume. A randomized trial suggested that cyclosporine was well tolerated and significantly more effective than the active control penotsanpolysulfate.
Claire Yang from Seattle and the Interstitial Cystitis Collaborative Research Network report on a randomized, double-blind, placebo controlled clinical trial of mycophenolate mofetil (MMF), an immunosuppressant drug with a reasonable safety profile, in patients with IC/BPS in whom previous therapy for this syndrome had failed. The agent was chosen because of the unavailability of a placebo for cyclosporine, an older drug available only in generic form. Primary trial objectives were to compare 2 grams MMF daily to placebo for effects on overall IC/BPS symptoms and well-being in patients with refractory IC/BPS, and assess the medication safety profile.
Only 58 out of an anticipated 210 patients had been randomized using a 2:1 randomization when the manufacturer issued a black box warning 6 month after the study had begun. The warning noted positive evidence of fetal risk and addressed the risk of susceptibility to infection and the possible development of lymphoma. Subject enrollment was suspended and an interim analysis identified decreased efficacy of MMF when compared to placebo. While numbers were small, the results did not indicate that further investigation of MMF would be fruitful.
The authors looked back on the trial to see what could be learned. MMF was reasonably well-tolerated. Recruitment was difficult primarily due to the exclusion criteria mandated for prior malignancies or premalignant conditions, including cervical dysplasia, colon polyps, and any skin cancer, including basal cell cancer. Finally, the rationale for selecting MMF was based on “less than solid reasoning.”
This author participated in the trial, and many of us were disappointed that we could not use cyclosporine for which there was good preliminary data, and which would be a relatively inexpensive therapy, being a generic drug and if the trial were successful. It was abandoned in favor of MMF, despite a lack of preliminary studies, in the hopes that the mechanism of action would be similar enough to show benefit, and with the availability of a placebo that would make the trial fit within the budget. The results, although negative, leave open the possibility that future immunosuppressive therapy trials may be worthwhile, and provide a cautionary message in the construction of future multicenter trial efforts.
Yang CC, Burks DA, Propert KJ, Mayer RD, Peters KM, Nickel JC, Payne CK, Fitzgerald MP, Hanno PM, Chai TC, Kreder KJ, Lukacz ES, Foster HE, Cen L, Landis JR, Kusek JW, Nyberg LM; Interstitial Cystitis Collaborative Research Network
J Urol. 2011 Mar;185(3):901-6
10.1016/j.juro.2010.10.053
PubMed Abstract
PMID: 21238993
UroToday.com IC/PBS/BPS/HBS Section
