Tumor necrosis factor inhibitors and risk of peripheral neuropathy in patients with rheumatic diseases

Abstract

ImportanceTumor necrosis factor inhibitors (TNFi) are widely used in the treatment of a variety of autoimmune diseases. A number of case reports have linked TNFi to neurologic adverse events including peripheral neuropathy (PN) in patients with rheumatic diseases. ObjectivesTo quantify the risk of peripheral neuropathy with TNFi in patients with rheumatic diseases. DesignNested-Case Control study within a cohort of patients with rheumatic diseases. SettingPharMetrics Plus™ health claims database from the United States. ParticipantsFrom a random sample of 9,053,240 subjects from the PharMetrics Plus™ database a cohort of patients with rheumatic diseases who had two physician visit codes for rheumatoid arthritis, ankylosing spondylitis and psoriasis in addition to a medication used in the treatment of each condition from 2006 to 2016 was created. ExposureWe created different risk periods of current use (day 0–60), recent use (day 61–180) and past use (day 180–365) from the index date. Main Outcome MeasuresNew cases of PN were identified from the rheumatic disease cohort. Each case was matched to 10 controls by calendar time and age using density based sampling. Rate ratios (RRs) for new users of TNFi were computed using conditional logistic regression adjusting for gender, vitamin B12 deficiency, fluoroquinolone use, HIV, viral hepatitis, chronic renal failure and diabetes. ResultsAmong a cohort of 61,570 patients with rheumatic diseases 1358 cases of PN and 13,580 corresponding controls were identified. The adjusted rate ratio (RR) of PN among recent users of TNFi was 1.14 (95% CI:0.90–1.43). The RR for past use of TNFi was 2.77 (95% CI:1.67–4.58). Past users who used three or more prescriptions had a higher risk of PN 3.49 (1.63–7.49). The RRs did not change when the risk of PN with TNFi was compared to those taking methotrexate and one additional disease modifying anti rheumatic drug (DMARD) for recent and past use (RR = 0.95 [95% CI:0.72–1.24] and RR = 2.30 (1.37–3.87), respectively). ConclusionsPatients with rheumatic diseases who are past users of TNFi are at higher risk of developing PN compared to those taking methotrexate and one additional DMARD.