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Analysis of Long-Term Elmiron Therapy for Interstitial Cystitis
VOIDING FUNCTION AND DYSFUNCTION, AND FEMALE UROLOGY
Editorial Comment: Since 35% of the patients did not return the case report forms and the expected placebo effect for subjective symptomatology ranges between 20 and 40?6, a randomized double-blind placebo controlled study clearly is necessary, as the authors suggest. Alan J. Wein, M.D. Intravesical Hyaluronic Acid in the Treatment of Refractory Interstitial Cystitis A. MORALES, L. EMEF~SON AND J. C. NICKEL, Department of Urology, Queen’s University, Kingston, Ontario, Canada Urology, suppl., 4 9 111-113, 1997 Objectives. On the assumption that interstitial cystitis (IC) is the result of a defective mucous lining of the bladder epithelium, a study was carried out to investigate the activity of hyaluronic acid (HA) in the treatment of IC. HA is an important glycosaminoglycan (GAG) present in all connective tissues, including the GAG layer of the vesical mucosa. It exhibits a variety of pharmacologic properties that enhance its appeal for the therapy of IC. Methods. A total of 25 patients, with the characteristic picture of IC and refractory to other medical treatments, participated in a trial of HA. Patients received 40 mg of HA intravesically on a weekly basis for 4 weeks, then monthly. Response to therapy was evaluated by symptom score, voiding diaries, and visual analog scales. Results. An initial positive (complete + partial) response of 56% at week 4 increased to 71% by week 12. This response was maintained until week 20; beyond week 24 there appears t o be a moderate decrease in the effectiveness of the medication. There was no significant toxicity attributable to the presence of HA in the bladder. Conclusions. The response of refractory IC patients to the intravesical administration of HA was gratifying. In the past, many therapies for IC that were initially considered promising failed the test of a controlled study. Further studies will establish the effectiveness of this particular preparation of HA in the treatment of IC.
Editorial Comment: This report also indicates that a subsequent randomized double-blind placebo controlled trial is necessary. Alan J. Wein, M.D. Intravesical Dimethyl Sulfoxide (DMSO) for Interstitial Cystitis-A Practical Approach J. PARKIN,C. SHEA AND G. R. SANT, Interstitial Cystitis Clinic, New England Medical Center and Department of Urology, Tufts University School of Medicine, Boston, Massachusetts Urology, suppl., 4 9 105-107, 1997 Objectives. To provide a brief overview of intravesical dimethyl sulfoxide (DMSO) therapy for interstitial cystitis and offer a practical approach to patient treatment. Methods. A review of the literature and a summation of the experience with treatment of >300 patients with DMSO at the Interstitial Cystitis Clinic, New England Medical Center. Results. DMSO is helpful in a significant number of patients and it has acceptable morbidity and an excellent safety profile. Conclusions. Intravesical DMSO (singly or in combination) is one of the mainstays in the pharmacologic treatment of interstitial cystitis. Editorial Comment: This concise report demonstrates 50 to 90% overall positive response rates in patients with interstitial cystitis. The overall relapse rate after a 4 to 8-week course of treatment ranges between 35 and 4 W but approximately50 to 600/0 of patients who had a relapse responded to additional intravesical treatments. Alan J. Wein, M.D. Analysis of Long-TermElmiron Therapy for Interstitial Cystitis P. M. -NO, Division of Urology, Temple University School of Medicine, Philadelphia, Pennsylvania Urology, suppl., 4 9 93-99, 1997 Objectives. The long-term efficacy and safety of Elmiron (oral pentosan polysulfate sodium) in relieving recurring symptoms of interstitial cystitis (IC) were investigated in a long-term, open-label physician’s usage study. Methods. Patients with diagnosed interstitial cystitis who met the study entry criteria received shipments ofElmiron for 3 months at a dose of 100 mg 3 times a day and for consecutive 3-month periods, provided they completed and returned questionnaires about their disease symptoms, reported any adverse events, and had laboratory data collected before each new shipment. Patients were required to purchase the medication. Responses to questionnaires provided the data reported here. Several symptomatic parameters of the disease (overall improvement, overall improvement in pain and urgency, urinary frequency, and nocturia) were recorded in this way and used to evaluate efficacy.
2253
2254
VOIDING FUNCTION AND DYSFUNCTION, AND FEMALE UROLOGY
Results. Elmiron usage was correlated with improvements in some symptoms, and these improvements increased with duration of treatment. Some symptoms were improved within 5 months, although most continued to show improvements in both severity rating and in percentage of positive responders over 1to 2 years. Populations of patients receiving extended treatment, some for >90 months, showed no further improvement or worsening in symptom values. Forty-six percent of patients dropped out of the study within the first 3 months of Elmiron treatment. The frequency of adverse events was <4%. The most notable adverse events were reversible alopecia, diarrhea, nausea, headache, and rash. Conclusions. Elmiron appears to be an efficacious long-term treatment for reducing a constellation of debilitating symptoms associated with interstitial cystitis in some patients. Patients with a positive response to Elmiron appear to maintain this response over time. Editorial Comment: Dr Hanno is quite careful in his choice of words. "These long term compassionate use data are extremely useful in terms of establishing both the relative safety of Elmiron* as well as the lack of tachyphylaxis in many patients who have noted long term symptomatic improvement over many months while taking the drug. The study does, however, as a result of the protocol designed, necessarily select out drug responders for analysis, thereby magnifying the overall response rate. The results of this long term physician's usage study, taken together with previous short term (3months), placebo control, double blind multicenter studies indicate that Elmiron is a well tolerated medication that may be beneficial in some patients for the relief of the pain of interstitial cystitis." Alan J. Wein, M.D. The Interstitial Cystitis Symptom Index and Problem Index M. P. O'LEARY, G. R. SANT,F. J. FOWLER, JR., K. E. WHITMORE AND J. SPOLARICH-KROLL, Department of Surgery, Harvard Medical School, Division of Urology, Brigham and Women's Hospital, Department of Urology, Tufts University School of Medicine, New England Medical Center and Center for Survey Research, University of Massachusetts, Boston, Massachusetts, and Graduate Hospital, Philadelphia, Pennsylvania Urology, suppl., 4 9 58-63, 1997 Objectives. To develop 2 brief self-administered indices for measuring lower urinary tract symptoms and their impact in patients with interstitial cystitis (IC). Methods. An initial set of questions was developed and evaluated in focus groups. The index was revised, shortened, and validated with patients diagnosed in 3 large urologic practices with experience in interstitial cystitis (N = 45). Controls were recruited from a group of healthy volunteers in a gynecology clinic (N = 67). Internal consistency, construct validity, and test-retest reliability were evaluated. Results. The IC symptom index and the IC problem index measure urinary and pain symptoms and assesses how problematic symptoms are for patients with interstitial cystitis. Psychometric performance of both instruments is good, with the symptom index demonstrating excellent ability to discriminate characteristics between patients and controls. Conclusion. Both indices should be useful in the evaluation and management of patients with IC and should be particularly useful in clinical trials of new therapies for this condition, where reliable, validated, and reproducible outcome measures are critically important.
Editorial Comment: New therapies continually become available for interstitial cystitis. Evaluation of treatment efficacy and comparisons of individual treatments are hampered significantly by the lack of reliable and valid outcome measures. The symptom and problem indexes described in this article have been designed to identify the most important voiding and pain symptoms, and to assess how problematic patients find them in the clearest and most concise manner possible. The indexes can be self-administered and are intended to be used together, since measures of symptom severity alone may not adequately describe the bothersome nature of the problem from patient perspective. The indexes are not intended to diagnose interstitial cystitis but, similar to the American Urological Association symptom score for benign prostatic hypertrophy, are designed to evaluate the severity of symptomatology and monitor disease progression or regression with or without treatment. Alan J. Wein, M.D. Quality of Life and Urinary Incontinence C. J. KELLEHER,L. D. CARDOZO AND P. M. TOOZS-HOBSON, Department of Urogynaecology, King's College Hospital, London, United Kingdom Curr. Opin. Obst. Gynaec., 7: 404-408, 1995 Abstract Printed in J. Urol., 156 2123, 1996
* Baker Norton Pharmaceuticals, Inc., Miami, Florida.
Editorial Comment: Since 35% of the patients did not return the case report forms and the expected placebo effect for subjective symptomatology ranges between 20 and 40?6, a randomized double-blind placebo controlled study clearly is necessary, as the authors suggest. Alan J. Wein, M.D. Intravesical Hyaluronic Acid in the Treatment of Refractory Interstitial Cystitis A. MORALES, L. EMEF~SON AND J. C. NICKEL, Department of Urology, Queen’s University, Kingston, Ontario, Canada Urology, suppl., 4 9 111-113, 1997 Objectives. On the assumption that interstitial cystitis (IC) is the result of a defective mucous lining of the bladder epithelium, a study was carried out to investigate the activity of hyaluronic acid (HA) in the treatment of IC. HA is an important glycosaminoglycan (GAG) present in all connective tissues, including the GAG layer of the vesical mucosa. It exhibits a variety of pharmacologic properties that enhance its appeal for the therapy of IC. Methods. A total of 25 patients, with the characteristic picture of IC and refractory to other medical treatments, participated in a trial of HA. Patients received 40 mg of HA intravesically on a weekly basis for 4 weeks, then monthly. Response to therapy was evaluated by symptom score, voiding diaries, and visual analog scales. Results. An initial positive (complete + partial) response of 56% at week 4 increased to 71% by week 12. This response was maintained until week 20; beyond week 24 there appears t o be a moderate decrease in the effectiveness of the medication. There was no significant toxicity attributable to the presence of HA in the bladder. Conclusions. The response of refractory IC patients to the intravesical administration of HA was gratifying. In the past, many therapies for IC that were initially considered promising failed the test of a controlled study. Further studies will establish the effectiveness of this particular preparation of HA in the treatment of IC.
Editorial Comment: This report also indicates that a subsequent randomized double-blind placebo controlled trial is necessary. Alan J. Wein, M.D. Intravesical Dimethyl Sulfoxide (DMSO) for Interstitial Cystitis-A Practical Approach J. PARKIN,C. SHEA AND G. R. SANT, Interstitial Cystitis Clinic, New England Medical Center and Department of Urology, Tufts University School of Medicine, Boston, Massachusetts Urology, suppl., 4 9 105-107, 1997 Objectives. To provide a brief overview of intravesical dimethyl sulfoxide (DMSO) therapy for interstitial cystitis and offer a practical approach to patient treatment. Methods. A review of the literature and a summation of the experience with treatment of >300 patients with DMSO at the Interstitial Cystitis Clinic, New England Medical Center. Results. DMSO is helpful in a significant number of patients and it has acceptable morbidity and an excellent safety profile. Conclusions. Intravesical DMSO (singly or in combination) is one of the mainstays in the pharmacologic treatment of interstitial cystitis. Editorial Comment: This concise report demonstrates 50 to 90% overall positive response rates in patients with interstitial cystitis. The overall relapse rate after a 4 to 8-week course of treatment ranges between 35 and 4 W but approximately50 to 600/0 of patients who had a relapse responded to additional intravesical treatments. Alan J. Wein, M.D. Analysis of Long-TermElmiron Therapy for Interstitial Cystitis P. M. -NO, Division of Urology, Temple University School of Medicine, Philadelphia, Pennsylvania Urology, suppl., 4 9 93-99, 1997 Objectives. The long-term efficacy and safety of Elmiron (oral pentosan polysulfate sodium) in relieving recurring symptoms of interstitial cystitis (IC) were investigated in a long-term, open-label physician’s usage study. Methods. Patients with diagnosed interstitial cystitis who met the study entry criteria received shipments ofElmiron for 3 months at a dose of 100 mg 3 times a day and for consecutive 3-month periods, provided they completed and returned questionnaires about their disease symptoms, reported any adverse events, and had laboratory data collected before each new shipment. Patients were required to purchase the medication. Responses to questionnaires provided the data reported here. Several symptomatic parameters of the disease (overall improvement, overall improvement in pain and urgency, urinary frequency, and nocturia) were recorded in this way and used to evaluate efficacy.
2253
2254
VOIDING FUNCTION AND DYSFUNCTION, AND FEMALE UROLOGY
Results. Elmiron usage was correlated with improvements in some symptoms, and these improvements increased with duration of treatment. Some symptoms were improved within 5 months, although most continued to show improvements in both severity rating and in percentage of positive responders over 1to 2 years. Populations of patients receiving extended treatment, some for >90 months, showed no further improvement or worsening in symptom values. Forty-six percent of patients dropped out of the study within the first 3 months of Elmiron treatment. The frequency of adverse events was <4%. The most notable adverse events were reversible alopecia, diarrhea, nausea, headache, and rash. Conclusions. Elmiron appears to be an efficacious long-term treatment for reducing a constellation of debilitating symptoms associated with interstitial cystitis in some patients. Patients with a positive response to Elmiron appear to maintain this response over time. Editorial Comment: Dr Hanno is quite careful in his choice of words. "These long term compassionate use data are extremely useful in terms of establishing both the relative safety of Elmiron* as well as the lack of tachyphylaxis in many patients who have noted long term symptomatic improvement over many months while taking the drug. The study does, however, as a result of the protocol designed, necessarily select out drug responders for analysis, thereby magnifying the overall response rate. The results of this long term physician's usage study, taken together with previous short term (3months), placebo control, double blind multicenter studies indicate that Elmiron is a well tolerated medication that may be beneficial in some patients for the relief of the pain of interstitial cystitis." Alan J. Wein, M.D. The Interstitial Cystitis Symptom Index and Problem Index M. P. O'LEARY, G. R. SANT,F. J. FOWLER, JR., K. E. WHITMORE AND J. SPOLARICH-KROLL, Department of Surgery, Harvard Medical School, Division of Urology, Brigham and Women's Hospital, Department of Urology, Tufts University School of Medicine, New England Medical Center and Center for Survey Research, University of Massachusetts, Boston, Massachusetts, and Graduate Hospital, Philadelphia, Pennsylvania Urology, suppl., 4 9 58-63, 1997 Objectives. To develop 2 brief self-administered indices for measuring lower urinary tract symptoms and their impact in patients with interstitial cystitis (IC). Methods. An initial set of questions was developed and evaluated in focus groups. The index was revised, shortened, and validated with patients diagnosed in 3 large urologic practices with experience in interstitial cystitis (N = 45). Controls were recruited from a group of healthy volunteers in a gynecology clinic (N = 67). Internal consistency, construct validity, and test-retest reliability were evaluated. Results. The IC symptom index and the IC problem index measure urinary and pain symptoms and assesses how problematic symptoms are for patients with interstitial cystitis. Psychometric performance of both instruments is good, with the symptom index demonstrating excellent ability to discriminate characteristics between patients and controls. Conclusion. Both indices should be useful in the evaluation and management of patients with IC and should be particularly useful in clinical trials of new therapies for this condition, where reliable, validated, and reproducible outcome measures are critically important.
Editorial Comment: New therapies continually become available for interstitial cystitis. Evaluation of treatment efficacy and comparisons of individual treatments are hampered significantly by the lack of reliable and valid outcome measures. The symptom and problem indexes described in this article have been designed to identify the most important voiding and pain symptoms, and to assess how problematic patients find them in the clearest and most concise manner possible. The indexes can be self-administered and are intended to be used together, since measures of symptom severity alone may not adequately describe the bothersome nature of the problem from patient perspective. The indexes are not intended to diagnose interstitial cystitis but, similar to the American Urological Association symptom score for benign prostatic hypertrophy, are designed to evaluate the severity of symptomatology and monitor disease progression or regression with or without treatment. Alan J. Wein, M.D. Quality of Life and Urinary Incontinence C. J. KELLEHER,L. D. CARDOZO AND P. M. TOOZS-HOBSON, Department of Urogynaecology, King's College Hospital, London, United Kingdom Curr. Opin. Obst. Gynaec., 7: 404-408, 1995 Abstract Printed in J. Urol., 156 2123, 1996
* Baker Norton Pharmaceuticals, Inc., Miami, Florida.