Newer OAB agent shows advantage in several outcomes

December 1, 2005

Montreal--Two newer-generation antimuscarinic agents—solifenacin succinate (VESIcare) and extended-release tolterodine tartrate (Detrol LA)—improve symptoms of overactive bladder, but solifenacin appears to provide superior outcomes, according to a trial conducted in collaboration with the manufacturer of solifenacin. Benefits of solifenacin appear to be due, at least in part, to the availability of two approved doses of the drug, researchers say.

Montreal-Two newer-generation antimuscarinic agents-solifenacin succinate (VESIcare) and extended-release tolterodine tartrate (Detrol LA)-improve symptoms of overactive bladder, but solifenacin appears to provide superior outcomes, according to a trial conducted in collaboration with the manufacturer of solifenacin. Benefits of solifenacin appear to be due, at least in part, to the availability of two approved doses of the drug, researchers say.

"We've been long waiting to see a comparison between these two new-generation antimuscarinics," said John Bolodeoku, MBBS, senior director of medical affairs and health economics at Astellas Pharma Europe, Ltd., Middlesex, England, the manufacturer of solifenacin. "The solifenacin-treated patients fared better than those on the treatment regime of tolterodine ER."

Dr. Bolodeoku presented the study results at the International Continence Society annual meeting here.

After 4 weeks, patients had the option to increase their drug dosage. Those in the solifenacin arm who chose to do so went up to 10 mg of the drug, but those in the tolterodine arm only added a placebo to their 4-mg dose because tolterodine is only recommended for use in doses of 4 mg, while solifenacin is recommended in doses of 5 mg and 10 mg.

The trial was designed to detect the non-inferiority of solifenacin compared with tolterodine using the primary endpoint of micturition frequency, which it achieved. An analysis of the primary and secondary endpoints was carried out as defined in the protocol, exploring a potential superior action of solifenacin over that of tolterodine on the basis of the numbers of micturitions, urgency episodes, incontinence episodes, nocturia episodes, adverse events, and pad usage per 24-hour period, as well as volume voided per micturition and proportion of patients who decided to increase their drug dose.

The trial also included a subjective outcome measure of patients' improvement in symptoms as measured by the Perception of Bladder Condition (PBC), a 6-point, validated, categorical scale.

"We've not only looked at what you'd call the traditional measures, which are urgency, frequency, micturition, volume voided, but at what the patients felt," Dr. Bolodeoku told Urology Times.

Incontinence episodes drop

After 4 weeks of therapy, 48% of patients taking solifenacin, 5 mg, and 51% of those taking tolterodine ER, 4 mg, opted to increase their drug dosage. By the end of the trial, solifenacin was found to be superior to tolterodine ER in terms of managing objective parameters of urgency, urge incontinence, incontinence, and pad usage.

The number of urgency episodes per 24 hours dropped from baseline by a mean of 2.85 with solifenacin and 2.42 with tolterodine ER (p=.035). The number of urge incontinence episodes dropped by a mean of 1.42 with solifenacin, compared with 0.83 with tolterodine (p=.001). The number of incontinence episodes dropped by 1.60 with solifenacin versus 1.11 with tolterodine (p=.006). Finally, patients on solifenacin used about 0.4 of a pad less in each 24-hour period than did those on tolterodine (p=.002).

Subjective results

In terms of patients' subjective analysis of symptom improvement, both drugs improved symptoms on the basis of PBC score. However, solifenacin was associated with significantly greater improvement represented by a mean drop in score about 0.2 points greater than that seen with tolterodine ER (p=.006).

"[In] the technical points which we look at, like urgency, incontinence (which we're used to), we see a significant difference between solifenacin and tolterodine," Dr. Bolodeoku said. "That is also borne out by the improvement that the patients perceive in their bladder condition."