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US Dept. of Health and Human Services
NIH News
National Institutes of Health

For Immediate Release
August 11, 2003

Interstitial Cystitis Study Finds Limited Benefit in Two Oral Drugs

An 18-month pilot study of two commonly available treatments has shown no significant benefit in patients with interstitial cystitis (IC). The results are reported in the September issue of the Journal of Urology.

The first in a series of treatment studies planned by the Interstitial Cystitis Clinical Trials Group tested the effectiveness of pentosan polysulfate sodium (Elmiron®) and hydroxyzine hydrochloride (Atarax®) in 121 patients with IC. Most volunteers reported experiencing moderate pain, discomfort and urinary frequency for at least a year before entering the study.

IC is a chronic, debilitating condition that affects about a million people, most of them women. Patients suffer pelvic, bladder, or perineal pain and the urge to urinate as often as 18 times a day. Available treatments are limited and not effective for everyone. The National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) initated the Clinical Trials Group in 1998 to identify useful therapies for this devitalizing and difficult disease with no known cause and no cure.

Elmiron® and Atarax® were chosen for early testing because patients prefer oral drugs and each drug has different mechanisms of action. Elmiron® is the only drug approved by the Food and Drug Administration for IC. Doctors do not know exactly how it works, but one theory is that it may repair defects that might have developed in the lining of the bladder. In some patients, mast cells are present in the tissue of the bladder wall, possibly a sign of an allergic or autoimmune reaction. Atarax®, an antihistamine previously untested in a randomized, placebo-controlled trial for IC, reduces mast cell activity. Mast cell activity can cause bladder inflammation and pain, and may play a part in IC.

Patients in the randomized trial received either Elmiron® or Atarax®, a combination of the two, or a placebo. Researchers hoped that a combination treatment might result in faster, more effective symptom relief. However, neither the drugs nor the combination therapy produced a statistically significant benefit in patients. Forty percent of the volunteers who took the combined treatment benefited. Elmiron® alone helped 28 percent of the patients in the trial, while 23% percent had a positive response to Atarax®. Side effects were minimal.

“We believe that IC may be caused by many factors,” says Leroy M. Nyberg, M.D., NIDDK’s Urology Program Director. “That would explain why some treatments work for certain patients but not others. It’s also possible that these treatments might work better for IC patients with less severe symptoms than those seen in the volunteers,” Nyberg adds.

Because these treatments proved ineffective for the majority of patients, researchers do not plan to expand the trial, ordinarily the next step if a pilot study is successful. They say, however, that they have gained useful information for future clinical trials in IC. The group has already recruited patients for its second treatment study, which is testing whether the bacterium Bacillus Calmette-Guerin (BCG), directly instilled in the bladder, relieves the pelvic pain and frequently urination that are hallmarks of IC.

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Our comments:

This study has already caused great confusion among patients. Perhaps we should not jump to a negative conclusion too quickly. This study has some flaws worth considering. The ICCTG was unable to recruit enough patients to participate. Only 96 patients actually finished the study. Indeed, one physician we contacted for comments discounted the results of the study entirely because of this. (Previous Elmiron studies which showed effectiveness had several hundred participants involved.) The data for hydroxyzine can also be questioned. Specifically, the target dosage was 50mgs but they chose to begin patients at a lesser dosage and slowly move them up to 50 mgs. Thus, they were not at the most effective dose during the duration of the study. Lastly, as Dr. Nyberg clearly states above, these drugs may have more effectiveness on patients with less intense IC.

We must remember that there appear to be many types (or subgroups) of IC. Some patients have just pain, while others have frequency & urgency. Some patients have mild symptoms, while others have more severe symptoms. Some patients appear to have more bladder wall damage (i.e. Hunners Ulcers), while others have less. Because these groups have yet to be thoroughly documented, it seems clear that some therapies could work more effectively for one type, and not the other. For example, Elmiron may be more effective in patients who have a bladder GAG layer problem where Hydroxyzine may be more effective for patients struggling with mast cell/histamine related inflammation in their bladder.

The good news is that there are many treatment options now available to patients. From newer medications such as RTX, BCG and Botox, to the older staples such as Elmiron, IC patients should know that there is hope. Even the alternative therapies grow more and more compelling. CystaQ, Cystoprotek, Algonot are all gaining rapidly in popularity with patients who have reported, anecdotally, some success. In our last guest lecture with Dr. Anderson, we also learned about how pelvic floor therapy can greatly reduce the symptoms of patients struggling with pelvic muscle tension and pain. Indeed, todays approach to therapy is now multi-modal. Patients are encouraged to consider a bladder coating, an antihistamine, an antidepressant and pelvic floor work.

This study also points out a rather desperate need. Had more patients been willing to participate, the data would likely be much more meaningful. The problem in patient recruitment probably stemmed from the fact that Elmiron was already commercially available. In either case, without willing patients and researchers, it will be extremely difficult to conduct further studies. We say "Bravo" and "Thank you" for those of you who did participate and we urge you, the patient, to consider participating in upcoming research studies if you (and your physician) feel that it would be wise for you to do so.