#5584 FIRST EXPERIENCES IN REAL LIFE WITH DIFELIKEFALIN IN GABAPENTIN RESISTANT UREMIC PRURITUS (CKDAP)
Authors: Manenti Lucio , Oliva Vincenzo , Pavone Laura , Motta Tommaso Di , Fiaccadori Enrico 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease associated pruritus (CKD-aP) has been recognized for over a century. The actual proposed off-label therapeutic option is gabapentin, that showed relevant efficacy in some small trial. Recently difelikefalin (DFK), a k-opioid receptor agonist, has been the first FDA and EMA approved drug for CKD-aP treatment. We report the first three treated patients suffering gabapentin- resistant CKD-aP in our dialysis center.

Method
Since March 2022, 2 patients have been treated with DFK. Before starting the treatment and every week thereafter until now, the patients completed the following scales: Worst-Itch Numerical rating scale (WI-NRS, 0 = no Itch, 10 = worst itch), and the sleep quality scale (SQS) (from 0 = worse to 10 = best quality).

Results
Case 1 (Male, 58 years-old). The patient started hemodialysis (HD) 5 years ago. He was suffering gabapentin resistant CKD-aP (WI-NRS 10, SADS = C, SQS = 3). As soon as DFK was available the patient started DFK 0.5 mcg/kg/every HD session. There was immediate and persistent treatment efficacy. After 1 month gabapentin was stopped and after 4 months of DFK therapy, WI-NRS = 0 and SQS = 10, in the absence of side effects. After 6 months DFK was stopped but 4 weeks later CKD-aP returned (WI-NRS 7, SQS = 7). DFK was administered again with immediate response (Fig. 1a).Case 2 (Female, 81 years-old). The patient started HD 5 years ago. Two years ago she started suffering moderate to severe gabapentin-resistant CKD-aP. Before starting DFK 0.5 mcg/kg/every HD WI-NRS = 6 and SQS = 3. In the next weeks we obtained a progressive reduction of CKD-aP. After 3 months WI-NRS = 3, SQS = 6. At 6 month follow up CKD-aP ameliorated significantly (Wi-NRS 0 and SQS = 9) (Fig. 1b). Case 3. (Male, 75-years old). The patient suffer initial dementia. He started hemodialysis 1 year ago. He presented with scratching lesions on his arms and legs and complained of itching. After an initial period treated with Gabapentin without success Difelikefalin was tried. At the first assessment WI-NRS 7 and SQS 5; after an initial apparent benefit the rating scales were particularly fluctuating. There was also a dissociation between the improvement of the scratching lesions and the persistence of high values on the WI-NRS (after 3 months WI-NRS = 8). At 6 months' follow-up the patient presented WI-NRS 9 and SQS 6 (Fig. 1c). The scratching lesions had almost disappeared.

Conclusion
Our initial experience with DFK in the treatment of CKD-aP in 3 gabapentin-resistant patients seems to recognize a remarkable efficacy of the drug. In particular, Case 1 showed a complete, immediate and lasting response, whereas no other drug had been able to improve very severe CKD-aP. Case 2 showed a slowly reduction but achieved complete response at 6 months. In Case 3 the improvement of the scratching lesions suggests a partial benefit of DFK, but to date no relevant results with the adopted scales has been achieved. In conclusion DFK seems to show promising efficacy particularly in CKD-aP resistant to gabapentin. In older patiants with cognitive problems the actual tools identified to measure CKD-aP seems inadequate.