An acute gout flare of the bilateral first metatarsophalangeal (MTP) joints was triggered by ibrutinib used for the treatment of chronic lymphocytic leukemia (CLL), according to findings from a case study published in Journal of Oncology Pharmacy Practice.

Bruton tyrosine kinase (BTK) inhibitors are important in the treatment of CLL and B-lymphoproliferative disorders, but some of the side effects of these drugs include thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, peripheral edema, and nausea. Ibrutinib has also been associated with atrial fibrillation, increased bleeding risk, and arthralgia/myalgia; however, gout has not been previously linked to any BTK inhibitor. 

In this report, the authors presented the case of a 65-year-old White man with CLL (Rai stage 0). His past medical history included chronic kidney disease stage 2 and gout involving the left first MTP joint, and a family history of Hodgkin lymphoma. No acute gout flare was reported in the previous 2 years; the disease was controlled with allopurinol 300 mg taken daily. 


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In March 2020, the patient presented with enlarging bilateral axillary lymph nodes causing discomfort, with an elevated white blood cell count (64.6 x 106/L) and platelet count (146,000 x 106/L). Following this, he received daily oral treatment with ibrutinib 420 mg due to worsening leukocytosis, uncomfortable axillary lymphadenopathy, new thrombocytopenia, and 11 q deletion on fluorescence in situ hybridization assay. The patient’s condition responded well to treatment, with normalization of platelet count and a decrease in leukocytes and axillary lymph nodes.

Four months after initiating treatment with ibrutinib, the patient developed severe pain, erythema, and swelling of bilateral first MTP joints, despite being compliant with prophylatic allopurinol. Bilateral foot x-ray showed soft tissue swelling and calcifications, suggestive of gout flares. The patient received treatment with ibuprofen 400 mg orally taken 3 times a day as needed for symptomatic relief; the patient’s symptoms subsided within 5 days. Allopurinol was continued and the ibrutinib dose was decreased to 280 mg orally daily. The patient was able to tolerate this dose without any subsequent events.

A causality assessment between ibrutinib and the gout flare via Naranjo nomogram questionnaire yielded a score of 6. Authors noted that this score could make the causality of the relationship between ibrutinib and gout probable. The mechanism by which this occurs remains to be determined.

“This rare side effect of ibrutinib therapy should prompt at least a dose reduction, if not cessation and switching to a different agent,” the authors concluded.

Reference

Kaur J, Tuler S, Dasanu CA.  Acute gout flare of bilateral first metatarsophalangeal joints due to ibrutinib use in chronic lymphocytic leukemia. J Oncol Pharm Pract. Published online July 5, 2021. doi:10.1177/10781552211029703