The Effect of Interleukin-1 Blockade on Persistent Complex Regional Pain Syndrome – an Open Trial

Background and Aims Patients with persistent CRPS suffer from long term pain, disability and this is associated with significant negative impacts on their physical wellbeing, mental health and social function. Treatments currently recommended aim to rehabilitate patients with pain reduction, physical/psychological interventions with the aim of an improvement in quality of life. Many patients gain only modest improvement and there is a significant demand for more effective treatments. Targeting the underlying mechanisms of CRPS may lead to improved outcomes. Methods INCA is a single arm open label feasibility study on the use of anakinra, an interleukin-1 receptor antagonist in patients with persistent CRPS. This is accompanied by two systematic reviews on CRPS immunotherapy and the use of quantitative sensory testing in CRPS. Patients with persistent CRPS were recruited between two tertiary pain management centres. They were offered daily self-administered subcutaneous injection of 100mg anakinra over a period of 120 days and measures of tolerability, pain, function, emotional distress, quality of life and limb sensitivity were measured. We also examined the tolerability of quantitative sensory testing in patients with CRPS as we noted high degree of pain sensitivity. Results 26 patients were recruited over 20 months and 24 completed the study at 120 days. The primary outcome of safety and tolerability was achieved, with no serious events, adverse events noted that was consistent with what was expected of the drug. There were small improvements in secondary outcomes such as pain intensity, function and emotional distress and quality of life. The Systematic review on immune therapies showed limited overall effect in immune modulation of CRPS but many of the studies were small and large randomised controlled trials were uncommon. QST in CRPS was reviewed which showed gain of function of pain pressure thresholds, and this progressed with disease duration. Other sensory measures showed changes but to a much lesser degree and this is a standout phenomenon observed in CRPS. Further examination of limb sensitivity with quantitative sensory testing found many patients poorly tolerate this due to the high degrees of limb sensitivity observed. Conclusion Anakinra was well tolerated in patients with persistent CRPS and the improvements in patient reported outcome measures suggest that this may justify further trials. Immune therapies however have failed to replicate these benefits so caution must be applied. Limb sensitivity has been highlighted as an important aspect of CRPS and this may be a potential biomarker of disease severity and progression.