Does immunotherapy treatment for CRPS have a future?

18 Months after the last patient completed their follow up, the long awaited results of the randomised trial of “Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome” (the LIPS trial) have been published.

As reported in December 2016 in Libby Parfitt’s excellent article, despite some people feeling that the trial definitely helped them, as a whole the trial was not a success. In their own words, it “was not effective in relieving pain in patients with moderate to severe CRPS of 1 to 5 years’ duration.”

As Libby explained, the purpose of the trial was “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.”

So, where does the failure of the LIPS trial leave immunotherapy generally as a potential treatment avenue for CRPS?

Immune modulators such as immunoglobulin work by selectively blocking mechanisms involved in the body’s inflammatory and immune response systems. Whilst a number of clinical trials of immune modulators have on a small scale provided optimistic results, that has not been replicated when scaled up and subjected to greater scientific rigour. The outcome of the LIPS trial is just the latest example of that.

However, despite the disappointing result of the LIPS trial, hopes for an immunotherapy breakthrough in the treatment of CRPS do remain alive.

Genetics

Even though two people may satisfy the Budapest Criteria for a diagnosis of CRPS does not mean that their symptoms and therefore their conditions are necessarily identical. Rather, a host of distinct clinical conditions, albeit with very similar presenting symptoms are, by virtue of the Budapest Criteria, grouped together under the CRPS banner. Researchers believe that it is likely that this variation, which is detectable genetically, is the reason there has been such disparity in response to various treatments.

Accordingly, the thought now is that whilst an immunotherapy breakthrough may be possible, greater scrutiny needs to be paid to the selection criteria for participation in future trials. This will almost certainly now include introducing new genetic criteria to ensure, as far as possible, homogeneity among participants. In short, to match the condition to the treatment.