Female vs male IBD patients more likely to cease TNF‐α inhibitor therapy due to side effects
Persistence to treatment with a tumour necrosis factor (TNF)‐α inhibitor for inflammatory bowel disease (IBD) appears to be lower among female than male patients, as reported in a recent study. Treatment discontinuation is driven mainly by side effects, the rate of which being higher in women than in men.
According to researchers, the observed sex differences may help clinicians make a more personalized treatment approach for female patients.
The analysis involved 529 patients (49.9 percent male) contributing to 631 treatment episodes (357 with infliximab, 240 with adalimumab and 34 with golimumab) and 2,280 TNF‐α inhibitor treatment years. Males were more likely to be treated with infliximab (69.3 percent vs 57.0 percent; p=0.003), whereas females were more commonly prescribed adalimumab (38.4 percent vs 27.3 percent; p=0.006) and more likely to receive a third TNF‐α inhibitor (3.4 percent vs 0.4 percent; p=0.003).
In total, 289 patients (45.8 percent) discontinued TNF‐α inhibitor therapy. The most common reason for discontinuation was secondary loss of response, followed by side effects. Frequently reported side effects were allergic reactions (28.6 percent), infections (19.0 percent), dermatological reactions (14.3 percent), and neurological (11.1 percent) and joint complaints (7.9 percent). [Aliment Pharmacol Ther 2019;50:386-396]
TNF‐α inhibitor discontinuation was significantly associated with female sex (adjusted hazard ratio [aHR], 1.42, 95 percent CI, 1.16–1.74), greater age at start of therapy per decade (aHR, 1.15, 1.04–1.27) and dose escalation (aHR, 3.74, 2.78–5.02).
In total cohort cause‐specific analysis, female sex was associated with only side effects as a reason for discontinuation (aHR, 4.05, 2.36–6.98). On the other hand, discontinuation due to secondary loss of response was related to the use of adalimumab (aHR, 1.70, 1.11–2.60) or golimumab (aHR, 4.97, 2.30–10.74) and dose‐escalation (aHR, 7.71, 5.28–11.26).
“Our data [also] show a trend towards an increased risk of discontinuation because of side effects in only [the] Crohn’s disease [population]. Interpretation of these results is difficult though and no previous literature has reported on this observation,” the investigators noted, adding that the current study was not designed to answer this finding and lacks power to reject or support it.
There is no clear explanation for why female sex is associated with reduced TNF‐α inhibitor drug persistence. However, previous reports indicate that females, in general, appear to have greater susceptibility to dose-related adverse drug reactions possibly as a result of several differences in pharmacokinetics and pharmacodynamics between males and females (eg, differences in percentage body fat or in hepatic clearance due to reduced or enhanced activity of cytochromes). [Expert Rev Clin Pharmacol 2014;7:469–485; Clin Pharmacokinet 2002;41:329–342]
Evidence also suggests that sex hormones interact with drug metabolism and mechanism of action, potentially leading to differences in efficacy and side effects of drugs between males and females. Other factors proposed to influence sex-related differences include a female predominance seen in functional pain syndromes, including functional bowel diseases, as well as disparities in healthcare‐seeking behaviour. [Trends Pharmacol Sci 2010;31:108‐114; Gastroenterology 2002;123:1686‐1701]
“Increasing awareness in doctors and educating female patients about side effects could potentially contribute to a reduction in drug discontinuation, although this remains to be shown in prospective studies,” the investigators said. “Additionally, we would recommend future clinical trials and postmarketing studies to give special attention to possible sex‐based differences in treatment outcomes.”