Desidustat Is Effective in Treating Pure Red Cell Aplasia Due to Recombinant Human Erythropoietin in Patients with Chronic Kidney Disease

Pure red cell aplasia (PRCA) following eryhtropoeitin (EPO) supplementation for anemia of chronic kidney disease (CKD) is rare but challenge to treat. Most cases of PRCA occurred in patients who received EPO alpha subcutaneously. Desidustat is an orally bioavailable, HIF-prolyl hydroxylase inhibitor, approved on March 2022 in India for the treatment of anaemia associated with CKD. The role of Desidustat in EPO induced PRCA is not known. Here we report a case series of PRCA induced by EPO and their successful treatment with Desidustat.

Fourteen consecutive PRCA patients developed while on EPO treatement for anemia of CKD patients from two hematology centres in south India were included in this analysis from May 2022 to May 2024.Thirteen of these patients were males. Twelve of these patients were on haemodialysis. Median age of presentation was 61 years (Range:51 to 69). Median Hemoglobin at the starting of EPO treatment for anemia of CKD was 7gram%. All these patients were receiving iron injection periodically if transferrin saturation was low. All except one patient had initial improvement in Hemoglobin to EPO treatment. Median rise in Hemoglobin from baseline after 4 months of EPO with or without IV iron was 2 grams%. All patients received generic EPO dose 4000 unit subcutaneously twice weekly. One patient had history of darbepoetin before receiving EPO. These patients had worsening of anemia requiring PRBC transfusion while on EPO needing hematology evaluation.

PRCA was diagnosed based on fulfilling following criteria: 1. Isolated severe normocytic normochromic anemia, 2. Low reticulocyte count, 3. Bone marrow aspiration showing increased myeloid erythroid ratio with reduced normoblastic erythroid, 4. No evidence of significant dysplasia in any lineage, 5. Biopsy showing normocellularity with decreased erythroid, 6. Glycophorin IHC showing reduced erythroids. All patients had chest Xray or CT ruling out thymoma. Anti EPO antibody was done in one patient only due to lack of readily available laboratory support.

The median duration from EPO initiation and PRCA diagnosis was 9.5 months (Range:2month to 38 months). Median Hemoglobin at the time of diagnosis of PRCA was 5.7gram% (range 3.2gm% to 8.6gram%). Median MCV was 83.4 femtolitre (range 76 -93). Median retic percentage was 0.2% (range 0.07 to 0.29). Median Erythroid colony percentage in bone marrow aspirate was 2.44% (Range from 1 to 6%). Two patients didn't receive any PRBC transfusion before the PRCA diagnosis. Rest 13 patients had multiple blood transfusion. Median blood transfusion before PRCA diagnosis while on EPO treatment was 9 (range 1-40). Four patients had failed prior immunosuppression therapy for PRCA (wysolone -2, wysolone followed by cyclosporine -1, Wysolone followed by cyclophosphamide 1). Median duration of immunosuppression therapy was 6 months (range 1 month to 11 months). One of these patients had sepsis and pulmonary tuberculosis while on immunosuppression. Desidustat was started as 2^nd line in these patients. For remaining 10 patients Desidustat was the first line of therapy.

The following states the dosing regimen of Desidustat: Starting dose of Desidustat was 100mg thrice weekly in 9 patients (64.3%) and 100mg daily in 5 patients (35.7%). Out of the nine patients with 100mg thrice weekly patients, 2 patients dose increased to 150mg thrice weekly, 2 patients dose increased to 100mg daily after 1 to 3 months.

Two patients were lost to follow up. In the remaining 12 patients, 9 patients had a response (64%), seen after median period of 4 months of starting Desidustat (range 3 to 8 months).Three patient was still transfusion dependent. Median Hemoglobin on last follow up in responding patients was 12.5gram% (range 8.5 to 13.6gram%). One patient had developed depression while on therapy. No other major side effects were observed. All 12 patients were last followed up in clinic between January and May 2024.

This case series points towards a potential drug repurposing of Desidustat in EPO induced PRCA in CKD in whom steroids, cyclosporine or other immunosuppression results in lot of side effects. Desidustat is useful in this setting with better tolerability. This study warrants further randomised control trial in these patients to assess optimal dose or schedule.

No relevant conflicts of interest to declare.

Desidustat ,approved in anemia due to chronic kidney disease.Here we are reporitng drug repurposing for Pure Red Cell Aplasia in chronic Kideny patients developed due to generic erythropoeitin supplementation.