EXPERIMENTAL AND THERAPEUTIC MEDICINE 12: 445-450, 2016
Treatment effect of cyclosporine A in patients with painful bladder syndrome/interstitial cystitis: A systematic review ZHIKUI WANG and LEI ZHANG Department of Nephrology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China Received January 25, 2015; Accepted February 4, 2016 DOI: 10.3892/etm.2016.3301 Abstract. Cyclosporine A (CyA) is emerging as a potential therapeutic strategy for painful bladder syndrome/interstitial cystitis (PBS/IC), which is currently an incurable disease. The purpose of this systematic review was to evaluate the treatment effects of CyA in PBS/IC. Electronic and manual retrieval procedures were carried out to identify eligible references for the systematic review. The entire contents of the included articles were assessed, from study design to reported results. Eight studies, comprising three randomized controlled trials (RCTs), four prospective studies and one retrospective cohort study, were included, involving a total of 298 subjects. Meta‑analysis was not implemented due to heterogeneity of the manner of reporting the outcome parameters. All studies reported an improvement in symptoms following treatment with CyA. The results of the three RCTs implied that the treatment effects of CyA were better than those of pentosan polysulfate sodium. Some adverse events, for example, elevation of serum creatinine levels and an increase in blood pressure, were noted in five studies. In conclusion, the evidence from the studies implied that treatment of CyA can result in a long‑term benefit in patients of PBS/IC; however, further evidence is required to verify this. Introduction Painful bladder syndrome/interstitial cystitis (PBS/IC) occurs far more frequently in women than in men. It has been reported that among 1.3 million Americans having the symptoms of PBS/IC, >1.2 million were women in the year 2007 (1). The typical age predilection is ~40 years (2). The common symptoms of PBS/IC include urinary urgency, frequency, nocturia and suprapubic or pelvic pain without any known etiological factor. Diagnostic criteria have been established by the National
Correspondence to: Professor Lei Zhang, Department of
Nephrology, Linyi People's Hospital, 27 Jiefang Road, Linyi, Shandong 276003, P.R. China E‑mail: [email protected]
Key words: cyclosporine A, interstitial cystitis, painful bladder syndrome, systematic review, treatment effect
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in order to standardize the diagnosis of PBS/IC; these include objective findings of glomerulations or Hunner's ulcer at cystoscopy and subjective symptoms of bladder pain or urinary urgency, in addition to multiple exclusion criteria such as age 2 years 10 6/4 58±13 2013 (11) prospective (some for up to 10 years). Exclusion: Use of angiotensin‑ converting enzyme inhibitors, angiotensin II antagonists, potassium‑containing drugs, any medicine that inhibits or induces CYP3A4, pregnancy, lactation, or regular intake of hypericin or grapefruit
First author, publication Study year (Refs.) Country type
Table I. Baseline characteristics of the included studies.
EXPERIMENTAL AND THERAPEUTIC MEDICINE 12: 445-450, 2016
447
Mean age (years) Regimen protocol
Fulfilled the NIDDK criteria 64 53/11, Case, Case group: 1.5 mg/kg CyA twice for IC. Exclusion criteria: History 56.2±14.7; daily (27 women, 5 men); control of cancer in the last 10 years, control, group: 100 mg PPS 3 times daily untreated hypertension or renal 59.7±13.0 (26 women, 6 men) insufficiency [serum creatinine higher than normal limits (>90 mg/dl in females or >100 mg/dl in males)]
Inclusion/ Gender exclusion No. of (female/ criteria subjects male)
General health perceptions; pain; emotional wellbeing; vitality; social functioning; physical capacity; sexual interest; sexual functioning
GRA; EGF, IL‑6; pain score (VAS); urinary frequency 24 h; mean voided volume; ICSI score
Frequency in 24 h; max awake bladder capacity; mean voided vol.; VAS; nocturia episodes; ICSI and ICPI symptom scores, GRA; PST
Outcome parameters
6 months
6 months
6 months
Follow up
N/A
N/A
Mild adverse events
Complications
CyA, cyclosporine A; CYP3A4, cytochrome P450 3A4; EGF, epidermal growth factor; GRA, global response assessment; HL Hunner's lesion; IC, interstitial cystitis; ICPI, O'Leary‑Sant Interstitial Cystitis Problem Index; ICSI, O’Leary‑Sant Interstitial Cystitis Symptom Index; IL‑6, interleukin 6; N/A, not available; NIDDKD, National Institute of Diabetes and Digestive and Kidney Diseases; NO, nitric oxide; PBS, painful bladder syndrome; PPS, pentosan polysulfate sodium; PST, potassium sensitivity test; RCT, randomized control trials; VAS, visual analog scale.
Sairanen, Finland RCT Fulfilled the NIDDKD criteria 64 51/13 Case, Case group: 1.5 mg/kg CyA 2009 (18) 53.2±11.9; twice daily; control group: control, 100 mg PPS 4 times daily 57.3±10.0
Sairanen, Finland RCT Fulfilled the NIDDKD criteria 37 32/5, Case, Case group: 1.5 mg/kg CyA 2008 (17) 55.7±14.8; twice daily; control group: control, 100 mg PPS 3 times daily 56.4±13.2
Sairanen, Finland RCT 2005 (16)
First author, publication Study year (Refs.) Country type
Table I. Continued.
448 WANG and ZHANG: TREATMENT EFFECT OF CYCLOSPORIN A IN PBS/IC
Sairanen, 2005 (16) Sairanen, 2008 (17)
Sairanen, 2005 (16)
Forsell, 1996 (15)
Improvement greater in the CyA group than in the PPS group, including general health perceptions, pain, emotional wellbeing, social functioning, physical capacity, limitation days, % of patients undertaking sexual activity (masturbation or intercourse)
Improvement: ‑2.2±1.6 in CyA group vs. ‑0.2±2.1 in PPS group (P
Treatment effect of cyclosporine A in patients with painful bladder syndrome/interstitial cystitis: A systematic review ZHIKUI WANG and LEI ZHANG Department of Nephrology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China Received January 25, 2015; Accepted February 4, 2016 DOI: 10.3892/etm.2016.3301 Abstract. Cyclosporine A (CyA) is emerging as a potential therapeutic strategy for painful bladder syndrome/interstitial cystitis (PBS/IC), which is currently an incurable disease. The purpose of this systematic review was to evaluate the treatment effects of CyA in PBS/IC. Electronic and manual retrieval procedures were carried out to identify eligible references for the systematic review. The entire contents of the included articles were assessed, from study design to reported results. Eight studies, comprising three randomized controlled trials (RCTs), four prospective studies and one retrospective cohort study, were included, involving a total of 298 subjects. Meta‑analysis was not implemented due to heterogeneity of the manner of reporting the outcome parameters. All studies reported an improvement in symptoms following treatment with CyA. The results of the three RCTs implied that the treatment effects of CyA were better than those of pentosan polysulfate sodium. Some adverse events, for example, elevation of serum creatinine levels and an increase in blood pressure, were noted in five studies. In conclusion, the evidence from the studies implied that treatment of CyA can result in a long‑term benefit in patients of PBS/IC; however, further evidence is required to verify this. Introduction Painful bladder syndrome/interstitial cystitis (PBS/IC) occurs far more frequently in women than in men. It has been reported that among 1.3 million Americans having the symptoms of PBS/IC, >1.2 million were women in the year 2007 (1). The typical age predilection is ~40 years (2). The common symptoms of PBS/IC include urinary urgency, frequency, nocturia and suprapubic or pelvic pain without any known etiological factor. Diagnostic criteria have been established by the National
Correspondence to: Professor Lei Zhang, Department of
Nephrology, Linyi People's Hospital, 27 Jiefang Road, Linyi, Shandong 276003, P.R. China E‑mail: [email protected]
Key words: cyclosporine A, interstitial cystitis, painful bladder syndrome, systematic review, treatment effect
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in order to standardize the diagnosis of PBS/IC; these include objective findings of glomerulations or Hunner's ulcer at cystoscopy and subjective symptoms of bladder pain or urinary urgency, in addition to multiple exclusion criteria such as age 2 years 10 6/4 58±13 2013 (11) prospective (some for up to 10 years). Exclusion: Use of angiotensin‑ converting enzyme inhibitors, angiotensin II antagonists, potassium‑containing drugs, any medicine that inhibits or induces CYP3A4, pregnancy, lactation, or regular intake of hypericin or grapefruit
First author, publication Study year (Refs.) Country type
Table I. Baseline characteristics of the included studies.
EXPERIMENTAL AND THERAPEUTIC MEDICINE 12: 445-450, 2016
447
Mean age (years) Regimen protocol
Fulfilled the NIDDK criteria 64 53/11, Case, Case group: 1.5 mg/kg CyA twice for IC. Exclusion criteria: History 56.2±14.7; daily (27 women, 5 men); control of cancer in the last 10 years, control, group: 100 mg PPS 3 times daily untreated hypertension or renal 59.7±13.0 (26 women, 6 men) insufficiency [serum creatinine higher than normal limits (>90 mg/dl in females or >100 mg/dl in males)]
Inclusion/ Gender exclusion No. of (female/ criteria subjects male)
General health perceptions; pain; emotional wellbeing; vitality; social functioning; physical capacity; sexual interest; sexual functioning
GRA; EGF, IL‑6; pain score (VAS); urinary frequency 24 h; mean voided volume; ICSI score
Frequency in 24 h; max awake bladder capacity; mean voided vol.; VAS; nocturia episodes; ICSI and ICPI symptom scores, GRA; PST
Outcome parameters
6 months
6 months
6 months
Follow up
N/A
N/A
Mild adverse events
Complications
CyA, cyclosporine A; CYP3A4, cytochrome P450 3A4; EGF, epidermal growth factor; GRA, global response assessment; HL Hunner's lesion; IC, interstitial cystitis; ICPI, O'Leary‑Sant Interstitial Cystitis Problem Index; ICSI, O’Leary‑Sant Interstitial Cystitis Symptom Index; IL‑6, interleukin 6; N/A, not available; NIDDKD, National Institute of Diabetes and Digestive and Kidney Diseases; NO, nitric oxide; PBS, painful bladder syndrome; PPS, pentosan polysulfate sodium; PST, potassium sensitivity test; RCT, randomized control trials; VAS, visual analog scale.
Sairanen, Finland RCT Fulfilled the NIDDKD criteria 64 51/13 Case, Case group: 1.5 mg/kg CyA 2009 (18) 53.2±11.9; twice daily; control group: control, 100 mg PPS 4 times daily 57.3±10.0
Sairanen, Finland RCT Fulfilled the NIDDKD criteria 37 32/5, Case, Case group: 1.5 mg/kg CyA 2008 (17) 55.7±14.8; twice daily; control group: control, 100 mg PPS 3 times daily 56.4±13.2
Sairanen, Finland RCT 2005 (16)
First author, publication Study year (Refs.) Country type
Table I. Continued.
448 WANG and ZHANG: TREATMENT EFFECT OF CYCLOSPORIN A IN PBS/IC
Sairanen, 2005 (16) Sairanen, 2008 (17)
Sairanen, 2005 (16)
Forsell, 1996 (15)
Improvement greater in the CyA group than in the PPS group, including general health perceptions, pain, emotional wellbeing, social functioning, physical capacity, limitation days, % of patients undertaking sexual activity (masturbation or intercourse)
Improvement: ‑2.2±1.6 in CyA group vs. ‑0.2±2.1 in PPS group (P
