Evaluation of tocilizumab-induced hypofibrinogenemia in rheumatology practice: a retrospective, real-life, single-center experience.

Abstract

Tocilizumab (TCZ) which is a humanized interleukin (IL)-6 receptor antibody has been increasingly widespread used in rheumatology practice. TCZ-related hypofibrinogenemia is a not well-described side effect, but awareness seems to be incresing as publications on this topic are also becoming more frequent. Our aim in this study was to determine the frequency, timing, and approach to TCZ-related hypofibrinogenemia in rheumatic diseases. We retrospectively screened our patients who received TCZ for inflammatory rheumatic diseases and studied serum fibrinogen at least once before and/or after drug administration. We recorded and analyzed demographic features (age, gender, diagnosis), comorbidities, laboratory parameters, management, and outcome data. 30 patients who received TCZ due to rheumatological diseases and had at least one fibrinogen level were included in this study. 73.3% were female and median age was found to be 65 (42-82) years, with median disease duration of 148 (36-500) months. 90% of the patients received TCZ for RA and 10% for GCA. We examined the fibrogen levels at an average of 24 months (min 1 max 108) following the start of TCZ treatment. The study group was divided into those with normal fibrinogen levels (normal fibrinogen group) and those with low fibrinogen levels (lowfibrinogen group). In total, hypofibrinogenemia was found in 14 (46.6%) patients. Median serum fibrinogen level in the low fibrinogen group after TCZ was calculated to be 151.5mg/dl (min 92 max 171). Most patients were asymptomatic (71.4%). Ecchymoses were in seen 4 (28,6%) patients. No major bleeding were seen. TCZ was discontinued in 5 out of 14 patients (35.7%), while 9 out of 14 patients (64.3%) were closely followed. Outcomes regarding fibrinogen levels (11 out of 14) were as follows: increase in 4 and not checked in one after cessation of the drug, 3 spontaneous increases under the drug, and 3 persistently low levels on TCZ treatment. We found no difference in terms of gender (p = 0.417), platelets (p = 0.343), ESR (p = 0.448), and CRP (p = 0.660) at the time of TCZ initiation between groups. TCZ-related hypofibrinogenemia is more frequent than expected with occurence in both the early and late stages of treatment. Further research is required to determine whether to regularly measure fibrinogen levels in patients using TCZ and how to treat patients with hypofibrinogenemia.