Interleukin-1 receptor antagonist treatment for Refractory CRPS (v1)
Research type
Research Study
Full title
Interleukin-1 receptor antagonist treatment for refractory complex regional pain syndrome
IRAS ID
288397
Contact name
Andreas Goebel
Contact email
Sponsor organisation
University of Liverpool
Eudract number
2021-000052-19
ISRCTN Number
ISRCTN12908996
Duration of Study in the UK
2 years, 0 months, 30 days
Research summary
Research Summary
Many patients who suffer from complex regional pain syndrome(CRPS) develop not only pain in the affected limbs but also swelling, colour changes, limited or abnormal movements and skin changes. In some patients, the condition is resistant to treatment and results in ongoing suffering and disability. While the reason why patients develop complex regional pain syndrome is not fully understood, we know from laboratory studies that inflammation caused by activation of the immune system plays a large role.
The purpose of doing this study is to see if complex regional pain syndrome can be treated by blocking a component of the immune system to reduce this inflammation. One component of the immune system that we believe plays an important part is a protein class called cytokines that activates the body’s inflammatory response in complex regional pain syndrome. This signal is a molecule called Interleukin-1 and blocking it using a drug called Anakinra has shown it to reduce symptoms in animal studies.
Anakinra is a drug that blocks Interleukin-1 from attaching to its receptors in the immune system. This reduces its ability to activate immune responses in the body. It is currently used in patients with chronic inflammation in their joints caused by rheumatoid arthritis. As complex regional pain syndrome also involves excessive inflammation that may be caused by abnormal activation of parts of the immune system it is thought that using Anakinra in CRPS would be effective in a similar manner.Summary of Results
This clinical trial aims to test a drug therapy for patients with complex regional pain syndrome (CRPS) with long term and persistent symptoms that did not respond to standard treatments. This drug, anakinra blocks a specific molecule that may be an important part of the of the immune response seen in patients with CRPS. Anakinra has been used in other autoimmune diseases and its effects and side effects are well known; however, it has not been used in CRPS and the aim of this trial was to assess its tolerability, effectiveness and our ability to recruit patients, which will give us information to set up possible future larger trials.
Anakinra was administered daily in an injectable form that patients were taught to use. Treatment was administered for 120 days and there was a final trial follow up done at day 180.
Two sites were involved in this trial, The Walton Centre in Liverpool and St Thomas' Hospital in London. The trial commenced in July 2022 and recruitment finished in March 2024. 26 patients were recruited (13 from each site) from 41 patients screened.
The primary outcome was to observe the number of serious adverse events (SAEs) and condition specific adverse events (AEs) experienced during the trial. There were no SAEs amongst registered participants; although, one patient who had consented to participate experienced an SAE prior to registration. One participant (3.8%) experienced three condition-specific AEs - one instance of an increase in CRPS associated pain and two instances of persistent pain at the injection site. Overall, the AEs were expected and mostly minor without the need for medical treatment. The most common events were pain at the injection site, nausea and headache which are well known side effects of this drug.
Retention to the clinical trial was high, only one participant was lost to follow up overall and 4 participants did not take the drug for 120 days. Two were due to the drug not being tolerated, one was the participant who was lost to follow up, and one had an increase in pain. Recruitment start was delayed in the early stages but was at the expected speed after start. The overall target was 30 patients and 26 were recruited.
Overall, pain was improved from 7.7 out of 10 at baseline to 5.3 out of 10 at the end of the 120 days. This is an approximate reduction of pain intensity by about a third on average.
During the period of drug administration, physical function, mood, anxiety and overall quality of life were better compared to before the drug was started. These improvements were variable among the participants, with some participants improving a lot and others only by a small amount. 3 participants felt worse with the drug, 8 participants did not note any difference and 14 were improved being on the drug; therefore, overall, more participants noted an improvement compared to participants who noted either no improvement or were worse.
Limb sensitivity was measured using a technique termed quantitative sensory testing will be analysed separately.
After the drug was completed at day 120, many of the benefits were diminished at day 180 follow up when no drug had been administered for 2 months.
In conclusion, the use of anakinra in CRPS was well tolerated and led to an overall improvement in health related outcomes which would justify further evaluation in a larger trial with a sham comparison (placebo); our anticipated recruitment speed was realisticREC name
Wales REC 3
REC reference
21/WA/0184
Date of REC Opinion
17 Sep 2021
REC opinion
Further Information Favourable Opinion