Mayo CLIPPERS Study Update

It must be Spring.

A very quick update/reminder about the CLIPPERS study at the Mayo Clinic. I had a very brief email conversation with Dr Tobin about the study recently. He confirmed that they are still actively recruiting and keen to collect data on as many patients as possible. In particular they are committed to tracking recruits at intervals in the future to gather information about outcomes. Treatment effectiveness, susceptibility to relapse and long-term effects of CLIPPERS are some of the big issues they want to study. They are also actively analysing the preliminary volunteer data they have already and will update us about this in due course. So if anyone is interested in finding out more about this study please look on the CLIPPERS repository page for more details.

Read other articles in this series at Living With CLIPPERS.


Living With CLIPPERS by Bill Crum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

Steroids - Short-term, medium-term or long-term?

It is now fairly well established in the research literature that for many (most?) people diagnosed with CLIPPERS, high-dose intra-venous corticosteroids (usually Prednisolone) followed by lower-dose orally administered treatment improves the condition. What to do after this initial treatment phase and how to manage the condition in the medium and long term is more debatable. What seems clear, is that some kind of continuing treatment is required. The most common reported variants involve tapering the steroid dose to a low level and then either :

1. maintaining the patient at that dose 
2. maintaing the patient at that dose together with another immuno-suppressant
3. tapering the steroid down to nothing and maintaining on another immuno-suppressant

A new case study discusses these issues in the context of a 63 year old man diagnosed with CLIPPERS. This patient was treated with option 2 above (80mg/day Prednisolone) and then Methotrexate (2.5mg/weekly). However he had complications on Methotrexate and was moved to Azathioprine (100mg/day) and Prednisolone (now 20mg/day). On this treatment, the patient had a good response and no CLIPPERS relapses for 18 months (and onward).

The interesting thing about this paper, is the authors consider the treatment in the context of somewhat related disorders like cerebral vasculitis. There, option 2 is maintained for 2-5 years to prevent relapse, and they suggest a similar treatment strategy may be necessary in CLIPPERS. Now, this week is my 2-year anniversary of first CLIPPERS symptoms and 1-year anniversary of coming off Prednisolone entirely (option 3 above). The authors of this paper also say that successful steroid discontinuation in CLIPPERS has not been reported. My 1-year off-steroid period is too short to be called successful, as others have had relapses after longer periods without Prednisolone. So caution is required, but so far, so good.

Read other articles in this series at Living With CLIPPERS.

Living With CLIPPERS by Bill Crum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

Long-term CLIPPERS

You can't escape it!

Just a quick post this time. I've been reading this recent paper about outcomes a bit more closely (see the last post for an overview). One of the 12 patients really stands out - a boy age just 13 years old when symptoms appeared (patient 5). This is much younger than most other cases but the really surprising thing is the duration of illness. He is listed as having had CLIPPERS symptoms for 408 = nearly 34 years; so those of us who think we have something new will have to take a step back and realise CLIPPERS has probably been around in unrecognised form a lot longer. This patient was recruited via a Multiple Sclerosis centre so perhaps had been regarded as an atypical MS patient for years. Unfortunately he also had the most relapses (12) over the follow-up period but was not treated with cortico-steroids. Interestingly he went for 280 months = 23 years without any relapses according to the graph in Figure 2. So all this suggests that CLIPPERS is survivable in the long-term but that appropriate treatment is key to keeping it at bay as far as possible ...

Read other articles in this series at Living With CLIPPERS.


Living With CLIPPERS by Bill Crum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

News Flash

The most important CLIPPERS paper of the year so far has just appeared. It's called "Long-Term Outcomes of CLIPPERS in a Consecutive Series of 12 Patients" by Dr Taieb and colleagues. I haven't had time to digest this paper properly as it is quite involved (and I'm not a doctor) but some very brief points from a first reading.

Back In Black

CLIPPERS Long-Term
(As usual, please note I'm not a doctor so don't take this as gospel.)

The paper focuses on the pattern of relapses in 12 people diagnosed with CLIPPERS, treated with cortico-steroids and followed over months or years. Dr Taieb says that "Secondary progression was not observed" - in Multiple Sclerosis secondary progression means "sustained build up of disability, independent of any relapses". So this study suggests that there isn't an underlying disease process continuing to cause damage after symptoms have been treated with cortico-steroids. This is good news.

Relapses
Patients who remained on steroid doses at 20mg/day or higher tended not to get relapses but patients who did get relapses continued to respond to repeated high doses of steroids. Dr Taieb found that early treatment of relapses was important to prevent worsening of symptoms during the relapse or continuing problems. So I guess it's good news that CLIPPERS remains treatable but not so good news that it can return after the first episode. We have to remember though that this is still only 12 patients so this paper represents an important step along the way rather than a definitive study.

Still Missing
One important missing piece of the puzzle is the effectiveness of alternative immunosuppressant therapy. Three of the patients described by Dr Taieb were moved on to Cyclophosphamide and one on to anti-CD20 (Rituximab) treatment with one subsequently relapsing. Of particular interest from my point of view is that there is no data on the long-term effectiveness of Azathioprine although there is some existing evidence (from other smaller studies) that Methotrexate can be effective.

I Am An Experiment

I have been on < 20mg Prednisolone / day since November 2011 and since June 2012 I have been taking only Azathioprine and am still well. So I guess we'll see what happens ....

Read other articles in this series at Living With CLIPPERS.

Living With CLIPPERS by Bill Crum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.