Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in February 2014. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

This evidence summary is based on 3 small randomised controlled trials (RCTs). All 3 of the studies were likely to be subject to significant bias and provide limited evidence on the use of dimethyl sulfoxide (DMSO) bladder instillation (Rimso-50) for interstitial cystitis.

Regulatory status: unlicensed.

This topic was prioritised because there was a high volume of requests from the NHS for information on this topic and potential for variation in practice.

Effectiveness

  • Assessing the effectiveness of treatments for interstitial cystitis is difficult due to a lack of certainty around the diagnosis and the use of subjective measures of response.

  • More people reported a 'marked improvement' with DMSO compared with placebo (6/15 [40%] compared with 3/17 [18%]; reported as statistically significant; no p value given) [1 RCT; n=33].

  • A Cochrane review included the RCT described above and provided additional statistical analysis not available in the published study. This showed no statistically significant difference between DMSO and placebo for bladder capacity and pain (1 RCT; n=33).

  • Statistically significantly more people reported to be 'much better' or 'completely cured' with DMSO compared with BCG (off-label use) [11/37 (30%) compared with 4/38 (11%); 1 RCT; 3 months; n=75].

Safety

  • The prescribing information for DMSO (Rimso-50; licensed by the US Food and Drug Administration) states that full eye evaluations including slit lamp examinations are recommended before and periodically during treatment.

  • Biochemical screening, particularly liver and renal function tests, and complete blood count should be done approximately every 6 months.

  • The British national formulary (December 2013) states that bladder spasm and hypersensitivity reactions may occur.

Patient factors

  • Administration may cause moderately severe discomfort, which may result in the inability to tolerate treatment.

  • May also cause garlic-like taste and odour on the breath and skin that may remain for 72 hours.

Resource implications

  • DMSO is unlicensed in the UK. No costs could be obtained from standard published sources or the manufacturer1.

  • Costs will also be associated with the administration of the bladder instillation.

1Informal sources suggest that the cost is around £101 (plus VAT) per 50 ml bladder instillation.

Key points

DMSO bladder instillation is unlicensed in the UK. It is available from 'special-order' manufacturers or specialist importing companies.

Three small RCTs were identified for inclusion in this evidence summary. One of the RCTs (Perez-Marrero et al. 1988) compared DMSO with placebo (saline) and 2 (Peeker et al. 2000 and Sairanen et al. 2009) compared DMSO with bacillus Calmette-Guerin (BCG) (off-label use). A Cochrane review on intravesical treatments for painful bladder syndrome/interstitial cystitis (Dawson and Jamison 2007) included 1 of these studies (Perez-Marrero et al. 1988). The Cochrane review also identified the Peeker et al. (2000) study, however the Cochrane review concluded that this study did not provide useful data for any outcome (see Evidence strengths and limitations).

Perez-Marrero et al. (1988) was a small randomised crossover trial that compared 4 instillations, 2 weeks apart, of DMSO (50 ml of 50% DMSO) with placebo (50 ml of normal saline) in 33 people (30 women; mean age 48 years) with biopsies suggestive of interstitial cystitis. After a 4-week washout period the treatment allocation was reversed and a further 4 instillations given. Assessment followed the completion of each treatment phase and comprised a subjective assessment by participants (rated as minimal [0], moderate or marked) and an objective outcome based on 3 urodynamic parameters. After completion of phase I, 40% (6/15) of people treated with DMSO reported marked subjective improvement in symptoms compared with 18% (3/17) of people receiving placebo. The difference in the proportion of people reporting marked subjective improvement was reported to be statistically significant but no statistical analysis was presented. People in the group that received DMSO at phase I continued to report subjective improvement after treatment with placebo at phase II.

The Cochrane review (Dawson and Jamison 2007) presented statistical analysis for 2 of the urodynamic parameters which was not available in the published study. This reported that there was no statistical significant difference between DMSO and placebo for maximum cystometric capacity (volume at which a person is unable or unwilling to tolerate continued bladder filling or leakage occurs) [mean difference 17.00 ml; 95% confidence interval [CI] −11.22 to 45.22] or number of people whose pain resolved at maximum cystometric capacity (23/28 compared with 22/28; odds ratio [OR] 0.22; 95% CI −1.10 to 1.55).

Sairanen et al. (2009) was a 3-month randomised open-label trial comparing intravesical instillations of 50 ml 50% DMSO with 50 ml Tice strain BCG (dose of BCG not reported, length of instillation not reported) given once a week for 6 weeks in 75 people (71 women; mean age 59 years) with painful bladder syndrome/interstitial cystitis. The main aim of this study was to evaluate a health-related quality of life questionnaire in painful bladder syndrome/interstitial cystitis. The primary outcome of the study was alleviation of pain. However, data for this outcome were not reported. Data were reported on subjective global assessment of treatment response. At the 3-month follow-up, more people had a global assessment of treatment response of 'much better' or 'completely cured' with DMSO compared with BCG (11/37 [30%] compared with 4/38 [11%]; p<0.05).

All 3 trials were likely to be subject to significant bias. None of them reported the method of randomisation, and whether or not randomisation was concealed was either not reported or unclear. In addition, the studies were either unblinded or blinded but at high risk of unblinding due to the characteristic garlic halitus (breath smelling of garlic) caused by DMSO bladder instillation.

In Perez-Marrero et al. (1988), 3 minor adverse events occurred (2 uncomplicated lower urinary tract infections, 1 case of biliary colic). It is unclear if these occurred during the placebo or DMSO phase. Two severe adverse events occurred during the placebo phase (1 hemiparesis, 1 migraine) but both completely resolved within 48 hours. In Peeker et al. (2000), adverse events reported following DMSO treatment were increased urinary urgency (2 cases) and dysuria (3 cases). Adverse events were not reported in Sairanen et al. (2009).

About this evidence summary

'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.

The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.

The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.