Evidence for Early Cyclosporine Treatment for Hunner Lesion Interstitial Cystitis

Vollstedt, Annah; Tennyson, Lauren; Turner, Katherine; Hasenau, Deborah; Saon, Md; McCartney, Teresa; Beck, Dana; Gilleran, Jason; Peters, Kenneth M.

doi:10.1097/spv.0000000000001108

Cited by 7 publications

(5 citation statements)

References 23 publications

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“…13,15 A strength of our study was the prospective long-term follow-up which allowed for rigorous monitoring of CyA efficacy as well as systematic control of blood pressure and creatinine values. While some studies reported creatinine variation over a few months only, 15,23 our study reinforced the safety of a prolonged CyA usage which is crucial considering that long-term treatment might be necessary to maintain relief. Moreover, there were no loss at follow-up and recall bias was avoided by conducting a longitudinal prospective follow-up.…”

Section: Discussionsupporting

confidence: 63%

“…Previous IC/BPS studies have reported hypertension and nephrotoxicity as the main adverse events with daily CyA doses of 2 or 3 mg/kg. [13][14][15] Recently, Vollstedt et al 23 reported that 24% of their cohort, receiving a fixed dose of 100 mg daily as maintenance treatment, experienced new or worsening in hypertension. This adverse event was reported in only 14% of our cohort, which may perhaps be explained by the dosage based on weight and the effort to taper down the dose (median daily dose of 80 mg).…”

Section: Discussionmentioning

confidence: 99%

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A pilot study on oral cyclosporine A in association with fulguration for the treatment of interstitial cystitis with Hunner's lesions

Brière

Bouchard

Ismail

et al. 2022

Neurourology and Urodynamics

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Aims To evaluate the efficacy and safety of lesion fulguration in combination with cyclosporine A (CyA) as a maintenance therapy in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) with Hunner's lesion (HL). Methods Retrospective observational study of refractory patients with HL treated with daily 1.5 mg/kg or less of oral CyA following lesion fulguration. Pain severity, subjective improvement, urinary symptoms, and adverse events were used to assess long‐term treatment efficiency and safety. Results Among the 22 patients, median follow‐up under CyA was 27 months. Patients reported sustained significant reduction compared to pretreatment in pain (0/10 vs. 8/10; p < 0.001), urinary frequency per 24 h (9.5 vs. 20.8; p < 0.001), and nocturia (2.3 vs. 7.6; p < 0.001). Subjective improvement rate (SIR) and patient global impression of improvement were of 90% and 1 (“very much better”), respectively, including four patients who considered themselves cured (SIR: 100%). Three patients needed an additional procedure due to pain relapse. Minor increase in creatinine was observed and three patients developed or worsened their arterial hypertension. CyA dosage was decreased to 1.2 mg/kg or less for long‐term relief (n = 8), creatinine increase (n = 5), and neutropenia (n = 1) with subsequent improvement in renal function without symptom deterioration. Conclusions Oral CyA seems to allow a sustained long‐term relief following HL fulguration by alleviating pain, decreasing urinary symptoms, and procuring great subjective improvement. The daily low dose of 1.5 mg/kg or less appears to have limited adverse events while preventing repeated procedures. Larger trials are warranted.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

A pilot study on oral cyclosporine A in association with fulguration for the treatment of interstitial cystitis with Hunner's lesions

Brière

Bouchard

Ismail

et al. 2022

Neurourology and Urodynamics

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“…GRO-KC elevation is consistent with the in ltration of neutrophils being a hallmark of acute in ammation and not chronic in ammation which typically de nes IC/BPS. However, acute in ammation is critical in the are up of symptoms in IC/BPS patients and therefore elevation of urinary GRO/KC may foreshadow the advent of acute in ammation that can be targeted with non-steroidal anti-in ammatory drugs to prevent the worsening of symptoms and avoid aggressive treatment with steroids and immune suppressants for the are up of IC/BPS (34)(35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

Temporally complex inflammatory networks in an animal model reveal signatures for interstitial cystitis and bladder pain syndrome phenotype

Shah,

Vodovotz,

Yoshimura

et al. 2023

Neurourology and Urodynamics

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Introduction and ObjectiveInterstitial cystitis and bladder pain syndrome (IC/BPS) presents with symptoms of debilitating bladder pain and is typically a diagnosis of exclusion. The cystoscopic detection of Hunner's lesions increases the likelihood of detecting tissue inflammation on bladder biopsy and increases the odds of therapeutic success with anti‐inflammatory drugs. However, the identification of this subgroup remains challenging with the current lack of surrogate biomarkers of IC/BPS. On the path towards identifying biomarkers of IC/BPS, we modeled the dynamic evolution of inflammation in an experimental IC/BPS rodent model using computational biological network analysis of inflammatory mediators (cytokines and chemokines) released into urine. The use of biological network analysis allows us to identify urinary proteins that could be drivers of inflammation and could therefore serve as therapeutic targets for the treatment of IC/BPS.MethodsRats subjected to cyclophosphamide (CYP) injection (150 mg/kg) were used as an experimental model for acute IC/BPS (n = 8). Urine from each void was collected from the rats over a 12‐h period and was assayed for 13 inflammatory mediators using Luminex™. Time‐interval principal component analysis (TI‐PCA) and dynamic network analysis (DyNA), two biological network algorithms, were used to identify biomarkers of inflammation characteristic of IC/BPS over time.ResultsCompared to vehicle‐treated rats, nearly all inflammatory mediators were elevated significantly (p < 0.05) in the urine of CYP treated rats. TI‐PCA highlighted that GRO‐KC, IL‐5, IL‐18, and MCP‐1 account for the greatest variance in the inflammatory response. At early time points, DyNA indicated a positive correlation between IL‐4 and IL‐1β and between TNF‐α and IL‐1β. Analysis of TI‐PCA and DyNA at later time points showed the emergence of IL‐5, IL‐6, and IFNγ as additional key mediators of inflammation. Furthermore, DyNA network complexity rose and fell before peaking at 9.5 h following CYP treatment. This pattern of inflammation may mimic the fluctuating severity of inflammation associated with IC/BPS flares.ConclusionsComputational analysis of inflammation networks in experimental IC/BPS analysis expands on the previously accepted inflammatory signatures of IC by adding IL‐5, IL‐18, and MCP‐1 to the prior studies implicating IL‐6 and GRO as IC/BPS biomarkers. This analysis supports a complex evolution of inflammatory networks suggestive of the rise and fall of inflammation characteristic of IC/BPS flares.

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“…Based on the presence of intense chronic inflammation in the HIC bladder, prior studies examined the utility of immunomodulatory therapies for patients with HIC; these include cyclosporine A or corticosteroids. To date, cyclosporine A has been the most frequent treatment for HIC, and it improves pain and urinary symptoms in refractory patients significantly [14] , [15] , [16] , [24] , [25] , [26] . However, the drug is associated with significant adverse events such as elevated serum creatinine levels, gingival hyperplasia, hypertension, and susceptibility to lymphoproliferative malignancies and skin malignancies [14] , [15] , [24] , [25] .…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Low-dose Oral Prednisolone for Patients with Refractory Hunner-type Interstitial Cystitis

Akiyama,

Niimi,

Nomiya

et al. 2023

European Urology Open Science

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Evidence for Early Cyclosporine Treatment for Hunner Lesion Interstitial Cystitis

Cited by 7 publications

References 23 publications

A pilot study on oral cyclosporine A in association with fulguration for the treatment of interstitial cystitis with Hunner's lesions

A pilot study on oral cyclosporine A in association with fulguration for the treatment of interstitial cystitis with Hunner's lesions

Temporally complex inflammatory networks in an animal model reveal signatures for interstitial cystitis and bladder pain syndrome phenotype

Efficacy and Safety of Low-dose Oral Prednisolone for Patients with Refractory Hunner-type Interstitial Cystitis

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