Imagine this clinical scenario: you have been presented with a two-year-old spayed female cat with her third episode of frequent painful urination and gross haematuria. Her owner explains the first episode occurred when they acquired a new puppy, which she hides from. The prior ultrasound was negative for uroliths, and her urine was culture negative. Haematology, serum biochemistry and urinalysis were unremarkable aside from the finding of large numbers of red blood cells in her urine sediment.
You explain to the owners that you suspect feline idiopathic lower urinary tract disease (FLUTD) (also known as feline idiopathic cystitis (FIC)) and probable bladder inflammation. After discussing with the owner that either non-steroidal anti-inflammatory drugs (NSAIDs) or steroidal anti-inflammatories (glucocorticoids) can be used to alleviate her clinical signs, the owners ask which you recommend.
Four studies were critically appraised, of which one was a retrospective cohort study, two were prospective double-blinded randomised studies and one was a prospective randomised study.
One small controlled trial (Osborne et al., 1996) compared prednisolone to a placebo. They found no clinical differences in dysuria or occult blood for cats diagnosed with idiopathic non-obstructive FLUTD hospitalised for 10 days and a clinical difference in time to a reduction in microscopic haematuria of 0.3 days. However, these results were not analysed for statistical significance and would likely have been underpowered to detect any significant difference. The study had a very small sample size, and clinical signs of feline cystitis may be exacerbated by stressful circumstances such as hospitalisation or diet change. Therefore the conditions for patients may not be applicable to cats discharged from hospital to their home environment.
Clinical signs of feline cystitis may be exacerbated by stressful circumstances such as hospitalisation or diet change
A second controlled trial (Dorsch et al., 2016) compared meloxicam to placebo in cats diagnosed with obstructive FLUTD. The authors applied statistical analysis to determine if there were significant differences in voiding behaviour (owner report only), general demeanour, haematuria, food intake and abdominal pain, as assessed by the veterinary surgeons during hospitalisation and owners at discharge. No statistically significant differences (P> 0.05) were calculated between the two treatment groups based on the owner questionnaire and veterinarian assessment, but small samples in each treatment group likely limited statistical power.
The third small controlled trial (Nivy et al., 2019) compared the recurrence of FIC-related clinical signs and recurrent urinary obstruction in cats at 10 days and one, two and six months after discharge. These patients were treated with phenoxybenzamine and alprazolam, with or without the addition of meloxicam. The authors found no statistically significant differences in the recurrence of obstructed or non-obstructed FIC for cats treated with either meloxicam or no meloxicam. However, subjective scoring of clinical signs was not detailed, and the study was underpowered for the actual obstruction rates reported.
The fourth paper (Hetrick and Davidow, 2013) was a retrospective cohort study that examined the association of different treatment factors with re-obstruction after 24 hours and 30 days. The study found no significant association between the use of meloxicam and the rate of re-obstruction at either time point but experienced high levels of incomplete or lost follow-up among the cases included.
In conclusion, no studies appear to provide evidence for steroid or NSAID use in decreasing clinical signs or the duration of clinical signs and recurrence rates associated with FLUTD. All studies had significant limitations in terms of statistical power, external validity and/or risk of bias, which limits the ability to show anything other than a large effect of treatment.
All studies had significant limitations in terms of statistical power, external validity and/or risk of bias
Osborne et al. (1996), Dorsch et al. (2016) and Hetrick and Davidow (2013) did not provide details of sample size calculation, nor did they present a power analysis. However, we can infer that statistical power was likely low. Nivy et al. (2019) performed a sample size calculation assuming a population with a much higher risk for FIC recurrence than actually occurred in their trial, thus a high risk for type II error was present.
Glucocorticoids are not considered analgesics, and there is insufficient evidence to suggest they provide a profound benefit in human interstitial cystitis. Although NSAIDs are considered a mainstay for the management of chronic pain, they are not considered a first-line treatment for FIC cases. There is a risk of numerous adverse gastrointestinal and renal side effects, including nephrotoxicity, gastric ulcers and gastric perforations in cats (Epstein et al., 2015). Given this, the current evidence does not propose that the use of NSAIDs shortens the duration of clinical signs of FIC.
The most effective treatment outcomes for FIC should focus on [multifactorial causes], with pharmacological drugs as an additional secondary action if required
Most research on the aetiology of FIC has focused on multifactorial causes, including (but not limited to) behaviour, housing, environment, diet, litter type, cohabitation with other cats or pets in the household, enrichment availability, anatomical formation, age, obesity, neuter states and even neurohormonal pathways (Segev et al., 2011; Kim et al., 2018; Cameron et al., 2004). The most effective treatment outcomes for FIC should focus on these factors, with pharmacological drugs as an additional secondary action if required.