Here’s some news that is just so 2016: the large-scale trial into the use of intravenous immunoglobulin infusions for CRPS has failed to show any benefit. It’s a cutting blow as this is one of the (very very few) potential new treatments that has got this far in testing.
The LIPS (low-dose intravenous immunoglobulin treatment for complex regional pain syndrome) trial involved 108 CRPS patients from all over the UK. All of them had moderate to severe pain and all had suffered from CRPS from 1 to 5 years. The trial offered each participant four infusions over a few months. The infusions were administered in hospital, and the drug was administered through a drip over several hours. Patients then had to keep a pain diary, recording how the infusion affected their CRPS pain.
For the first two infusions, neither the medical team running the trial nor the participant knew whether they were getting the real infusion of immunoglobulin or a placebo. Trials are double blinded like this (i.e. both participant and doctor are ‘blind’ about what they’re giving / receiving) as previous research has shown that the outcome of a trial can be unconsciously influenced by a doctor who knows that a patient is getting the ‘real stuff’. Again, if a patient believes they’re getting a real drug then it will unconsciously mean that they have a more marked reaction to it, regardless of whether it actually is real or a harmless placebo. Interestingly, research on this ‘placebo effect’ also shows that a red pill is more effective than a blue pill, and that the bigger the medical intervention, the bigger the impact it will have. That means that if I gave you the red pill and you felt a bit better, if I later gave you an injection then you’re likely to feel loads better, regardless of whether either of these treatments contained any medicine at all. Although if you’re letting me inject random stuff into you, you’ve probably got bigger problems to worry about than the placebo effect!
After the first two infusions, each patient was then offered the chance to have two ‘open label’ infusions, where, regardless of what happened in the double blind phase, they could try the real infusions of immunoglobulin. This large-scale trial was based on solid evidence from much smaller trials with CRPS patients. A previous test with 11 CRPS patients had shown that 5 of them had pain relief more than 25%. Results from that trial generally lasted around 5 weeks. That may not sound like a huge result, but ask any CRPS patient and they’d see even a 1% reduction in their pain over several weeks as a success. Thus the LIPS trial had a few different aims; they wanted to see if they could achieve a significant decrease in a significant number of patients’ pain and they wanted to see if they could make that decrease last.
They also wanted to see if the treatment could confirm something that CRPS doctors have suspected for a while: that the role of the immune system in creating and maintaining CRPS is more significant than we’d previously thought. Immunoglobulin works on the immune system in a variety of ways. It’s already regularly used as a treatment in autoimmune conditions like multiple sclerosis and lupus. If immunoglobulin worked really well on people with CRPS then it would open up a whole new avenue for exploration of potential treatments. So as you can see, there was a fair bit riding on this trial.
Sadly, although there are individuals who feel that the trials helped them, at a national level the trial has been declared a failure. The infusions simply didn’t help as many people as much as they hoped. It means that this line of treatment may be at a dead end now.
I took part in the trial myself and I’ve spoken to some other CRPS patients who did too. For me it was no help. Interestingly, after my first infusion my pain definitely did decrease, but after the second and third infusions there was no noticeable benefit. I also had some horrible side effects. I was sick to my stomach after every infusion which was difficult when I had a two hour car journey across London to get home. Each infusion caused a spike in my pain that would leave me sleepless for at least one night.
I also developed terrible stomach pain after each infusion; pain so bad it made me faint. It appears that my stomach lining disappeared during these periods, leaving my stomach unprotected from gastric acid. Several months later an endoscopy indicated that my stomach was still very inflamed and I continue to experience problems now, over a year later. I actually only went through with three infusions because of this stomach problem; I was getting married shortly after the day I was scheduled to have the final infusion, and I simply couldn’t cope with the CRPS and gastric issues in the run up to my wedding.
There are more positive stories from other patients though, patients who report a definite benefit from the infusions and are very sad that this treatment will no longer be pursued. It seems to me like these results mirror those of the original small-scale study, where some patients reported a significant (to them) decrease in their CRPS pain, whilst more than half found no concrete benefit at all. I’m saddened that the trial is negative as I was hopeful for a new treatment for this life-destroying illness. When I realised it wasn’t helping me, I was still hopeful that my participation in the study would pave the way for a treatment that might help others. It looks like that won’t be happening.
So what does the future hold for CRPS research? Well it’s not all doom and gloom, thank god. Neridronate, the treatment I wrote about a few weeks ago, has just received designation as a ‘Breakthrough Therapy’ for CRPS in the USA. This means that its development will be expedited as it has been recognised as a treatment that may offer substantial advantages for patients compared to the treatment options already available. It also means that patients in the USA will hopefully get to try it soon. This is great news and it might just be a fantastic Christmas present for every CRPS sufferer out there. Maybe not something you’ll find under your tree in 2016, but who knows where we might be by the end of 2017 or 18. Watch this space.
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Mycophenolate Treatment for CRPS – early results encouraging