Tuesday, 8 July 2014

Natalizumab treatment results in improved bladder function

Treatment with natalizumab results in a spontaneous improvement in bladder function. #MSBlog #MSResearch

"The open-label study below shows that in MSers with more advanced disease (mean EDSS 4.6) and active MS that starting on natalizumab resulted in an improvement in bladder function. This is an open-label study and hence there could be a superimposed placebo-effect accounting for all of, or some of, the positive effect. This data, however, mirrors our clinical experience with natalizumab and is supported by other data showing that about a third of MSers starting natalizumab notice an improvement in disability. Why? I suspect that by switching off inflammation it allows the nervous system to repair itself. This is an example of repair, albeit self-repair at work. It also suggests that for reparative, or remyelination, strategies to work in MS we are going to have to switch off the inflammatory component of this disease first. If we don't, any repaired myelin sheaths or nerve fibres are likely to get damaged in the next round of inflammation. This is why reparative strategies have to be added on to treatments that halt the disease process."

"As this data is not class 1 evidence, I have asked Biogen-Idec to look at the data from the placebo-controlled phase of their pivotal trial to see if MSer randomised to natalizumab had fewer bladder related adverse events, for example UITs, and whether or not they required less concomitant medication to treat  bladder symptoms. If the data shows this then this will support the strategy of early effective treatment to prevent, or at least delay bladder dysfunction in MS. The question is whether or not other treatments have the same effect as natalizumab."




Khatri et al. The TRUST (EvaluaTion of Bladder Function in Relapsing-Remitting MUltiple Sclerosis Patients Treated with Natalizumab) Observational Study. Int J MS Care. 2014 Spring;16(1):40-7.

Background: Bladder dysfunction is a common symptom of MS. This study was designed to evaluate effects of natalizumab on bladder function in RRMSers. 

Methods: The TRUST (EvaluaTion of Bladder Function in Relapsing-Remitting MUltiple Sclerosis Patients Treated with Natalizumab) study was an open-label, single-arm, two-center study. Natalizumab-naive MSers with disabling bladder dysfunction and initiating natalizumab were enrolled and followed for 6 months. The primary endpoint was change in the Urogenital Distress Inventory short form (UDI-6) score from baseline. Change in Incontinence Impact Questionnaire short form (IIQ-7) score from baseline was a secondary endpoint. 

Results: Thirty MSers were enrolled. Mean baseline characteristics were age 49.9 years, Expanded Disability Status Scale score 4.6, number of relapses in previous year 2.4, UDI-6 score 10.4, and IIQ-7 score 12.3. Mean changes in UDI-6 and IIQ-7 scores were significantly improved from baseline beginning at week 4 and up to week 24; mean improvements at 24 weeks were 4.4 (P < .0001) and 4.9 (P = .0005) points, respectively. At week 24, 85.7% and 78.6% of patients demonstrated improvements from baseline in UDI-6 and IIQ-7 scores, respectively. 

Conclusions: Incontinence-related quality of life as measured by UDI-6 and IIQ-7 scores improved significantly during natalizumab treatment.

CoI: multiple

3 comments:

  1. You wrote:
    "Urinary tract infections (UTIs) are the most common reason for MSers to be admitted to hospital."


    From: No, Urine Is Not Sterile - Huffington Post
    Hilt EE, et al 2014 (doi: 10.1128/JCM.02876-13) found whole swaths of bacteria not detected before in healthy urine, simply because no one had ever looked.

    The urine in the study came from patients at a clinic, including some with overactive bladder, a disorder that causes the sudden, frequent and urgent need to pee. Some bacteria seen in the study were more common in patients with overactive bladder than in women without urinary issues, suggesting these germs may play a role in the disorder.

    "We don't know if they're a consequence of overactive bladder or if they are a cause of overactive bladder," Hilt said. "We still have to perform more studies."


    Among the bacteria discovered was Actinobaculum schaalii, which is known to sometimes cause infections in the lower urinary tract (though the women in this study did not have urinary tract infections). Another was Aerococcus urinae, which can cause urinary and heart infections, particularly in the elderly.
    End of citation.

    Are we looking at the bacteria in the urine of MSers?
    Are bacteria (virus?) a consequence or are they the cause of the overactive bladder in MS?

    ReplyDelete
  2. Prof G based on this study and the other studies you are referring to would classify natalizumab treatment as being neurorestorative then?

    ReplyDelete
    Replies
    1. Re: "Prof G based on this study and the other studies you are referring to would classify natalizumab treatment as being neurorestorative then?"

      Yes, I would. It all depends how you define restoration of function. If you define it using the EDSS then most of the highly-effective treatments are neurorestorative. I doubt if they are doing the job themselves; all they doing is switching off the shredder and allowing endogenous or self-repair to occur. What is important to realise that the ability to self-restore depends on age and the amount of reserve capacity left behind. This is why I am advocating early effective treatment.

      The cynics who read this response will disagree; what they want is a mechanism of action that is clearly neurorestorative independent of suppressing inflammation. I am more pragmatic; we should view the emerging data on recovery of function on highly effective therapies as a step in the right direction. At least we are beginning to think about recovery, rather than fixating on simply slowing down worsening disability.

      Delete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.