Leflunomide-Associated Pancytopenia With or Without Methotrexate

Abstract

The risk of pancytopenia during leflunomide therapy appears to be increased when the drug is combined with methotrexate and in older patients. Onset may be delayed, and ongoing monitoring of blood counts is essential.

Induction of hyperchromic microcytic anaemia by repeated oral administration of methotrexate in rats

“…As female rats were more sensitive to MTX-induced anaemic changes than male rats, leukocytopenia was observed only in female rats. These changes were consistent with the data obtained from patients suffering from anaemia and pancytopenia and who were taking MTX during therapy (Chan et al, 2004;Cohen et al, 2005;McEwen et al, 2007). Interestingly, MTX caused an inverse effect on platelet, i.e.…”

“…Individual clinical data show that female patients are more likely to be affected than male patients (Chan et al, 2004;Lim et al, 2005), however those should be interpreted carefully as woman is generally liable to rheumatoid arthritis. Nevertheless, an earlier assessment would be important for therapeutic indications for which patient populations are at higher risk of pancytopenia, e.g.…”

“…The anti-inflammatory effects exerted by MTX are related to the increase in extracellular adenosine and its interaction with specific cell receptors; MTX inhibits AMP deaminase and adenosine deaminase (ADA) via a relative increase in the levels of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) (Cutolo et al, 2001). The major side effects of MTX treatment are the development of drug-resistant tumour cells (Fotoohi et al, 2004;Sorich et al, 2008), gastrointestinal toxicity (May et al, 1995;Vardi et al, 2008), bone marrow toxicity (Ermens et al, 1989;May et al, 1995;James et al, 2000;Belur et al, 2005), and pancytopenia (Chan et al, 2004;Cohen et al, 2005;McEwen et al, 2007) Anaemia is one of the most significant prognostic factors of MTX toxicity among patients with cancer or rheumatoid arthritis during the treatment period (Han et al, 2007;Dubsky et al, 2008). However, haematological changes along with bone marrow cytology have not been documented in rats, and limited data is available from studies using unilaterally nephrectomised rats treated with MTX that show the progression of severe anaemia in the absence of reticulocyte adaptation (Murakami et al, 1998).…”

The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases

“…Methotrexate and leflunomide inhibit cell replication, and leukopenia can be a side effect of their administration (36,116,117). One of us has previously suggested that myelosuppression forms a part of the action of methotrexate as a DMARD (86).…”

Pancytopenia, including macrocytic anemia, associated with leflunomide in a rheumatoid arthritis patient

“…13,14 Chan et al suggested that the risk of myelotoxicity associated with lefl unomide was increased in older patients (median age, 65.5 years) and on administering a combination of lefl unomide and MTX. In the present case, although the patient was elderly, lefl unomide and MTX were not administered simultaneously.…”