Oral cyclosporine can offer a safe and effective treatment option for refractory interstitial, even in patients who have been on chronic narcotic medications and particularly in those with Hunner’s lesions, according to the findings of a study presented by Cleveland Clinic urologists at the 2016 AUA annual meeting in San Diego.
San Diego-Oral cyclosporine can offer a safe and effective treatment option for refractory interstitial (IC), even in patients who have been on chronic narcotic medications and particularly in those with Hunner’s lesions, according to the findings of a study presented by Cleveland Clinic urologists at the 2016 AUA annual meeting in San Diego.
“Cyclosporine has known efficacy for treating recalcitrant IC and is listed in the AUA guideline as a fifth tier therapy. Yet, urologists are often reluctant to prescribe cyclosporine because they are concerned about toxicity,” said first author Daniel Shoskes, MD, MSc, director of the Novick Center for Clinical and Translational Research, Glickman Urological and Kidney Institute, Cleveland Clinic, and professor of surgery at Cleveland Lerner College of Medicine, Case Western Reserve University, Cleveland.
“Our experience shows that cyclosporine can be used safely with proper monitoring and can provide dramatic responses for some ‘end-stage’ IC patients. Hopefully, dissemination of this information will increase urologists’ comfort with cyclosporine and its use,” Dr. Shoskes added.
Dr. Shoskes and colleagues evaluated the efficacy and safety of a 3-month course of cyclosporine for treatment of refractory IC in a study that enrolled 26 patients over a 2-year period. Patients were eligible for participation if they had an Interstitial Cystitis Symptom Index (ICSI) score >9 and had failed at least two prior classes of therapy. Median duration of symptoms for the enrolled cohort was 66 months, and nine (35%) patients were using narcotic medications for symptom relief.
Cyclosporine was initiated at 3 mg/kg in divided doses twice daily, and dose adjustments were made based on measurement of the serum cyclosporine level measured 2 hours after the morning dose (C2).
“Monitoring of the C2 level rather than the trough level is the gold standard in transplant medicine because it better reflects total exposure,” Dr. Shoskes explained.
Twenty-one patients completed 3 months of treatment and 17 patients were seen at a post-treatment visit 1 to 2 months later. Responses were assessed using both the 7-point global response assessment (GRA) and ICSI. Mean scores of both instruments were improved by the 1-month visit and the benefit was maintained at 3 months, but it did not persist after cyclosporine was discontinued.
At 3 months, 11 (52.4%) patients showed response by GRA and eight (38.1%) patients achieved >30% improvement in their ICSI score. The mean ICSI score was significantly reduced from 14.9 to 11.7.
“These response rates are somewhat modest, but then these were patients who had failed all other interventions,” Dr. Shoskes said.
Next: >30% ICSI improvement in Hunner's patients
Subgroup analyses showed no significant difference in improvement on GRA for patients who were on chronic narcotic medication. Improvement of >30% in the ICSI score was achieved by all four of the evaluable patients who had Hunner’s lesions versus in 23.5% of the 17 patients without Hunner’s lesions, and the difference in the response rate between these two subgroups was statistically significant. Symptom improvement did not correlate with C2 levels or with any UPOINT domain.
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Safety monitoring included measurement of serum creatinine and nuclear glomerular filtration rate (GFR). Serum creatinine did not change significantly. Although there was a statistically significant decrease in mean nuclear GFR from baseline to 3 months, the value returned to baseline after cyclosporine was discontinued.
Cyclosporine was discontinued in one patient who developed hypertension after 2 months and one patient developed hyperglycemia. Monitoring of the C2 levels resulted in dose reduction in 11 patients, including the patient who developed hyperglycemia. Mean cyclosporine daily dose was 239 mg at the start of the study and 191 mg at 3 months.
“Most people on cyclosporine will show minimal serum levels at trough, but with C2 measurement we found the serum concentration was high in several patients,” noted Dr. Shoskes. “Use of a lower dose did not compromise response to cyclosporine, but may explain why we had a low incidence of side effects.”
Dr. Shoskes serves as a consultant/adviser for Astellas Pharma and Farr Labs.
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