TNF Inhibitor Drug-Induced Lupus Save

A study from the FDA's adverse event reporting system (FAERS or Medwatch) database identified cases of drug induced systemic lupus erythematosus (SLE) in patients receiving tumor necrosis factor-α (TNF-α) inhibitors - a paradoxical reaction to common antiinflammatory biologic agents.

Tumor necrosis factor-alpha inhibitors in this study included infliximab (INF), adalimumab (ADA), etanercept (ETN), golimumab (GOL), and certolizumab pegol (CZB); with these primarily being prescribed to treat rheumatoid arthritis (RA), ankylosing spondylitis (AS), inflammatory bowel disease (IBD), psoriasis (PsO), or other autoimmune diseases. Using the Standardized MedDRA Query (SMQ), adverse drug reaction (ADR) reports related to SLE of infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol were collected from the FAERS database starting from the data retrieval quarter up to the fourth quarter of 2023.

Adverse event risks were explored by signal detection using the Reporting Odds Ratio (ROR) method and the Bayesian Confidence Interval Propagation Neural Network (BCPNN) method. 

They identified a total of 12,080 reports of TNF-α inhibitors-induced SLE, with over 90% having serious or life-threatening outcomes and death.  While analyses of adverse events reported to the FDA can be hampered by significant reporting biases, this is the largest cohort of TNFi drug induced lupus yet reported.

Key takeaways from this analysis include:

• Deaths were seen with all 5 TNFi; but more deaths were reported with certolizumab pegol and etanercept. 
• Time to Lupus onset differed:
  • Longer (>7 months) for infliximab, adalimumab, and etanercept
  • Shorter (~2 months) for golimumab and certolizumab pegol.
• Strenth of association ranked as infliximab > adalimumab > certolizumab pegol > golimumab > etanercept.
• Drug specific notable findings 
  • More SLE arthritis in subgroup of males with adalimumab
  • Lupus nephritis risk associated with etanercept in the children (0–14 years)
  • Rare and severe lupus pericarditis and lupus pleurisy associated with infliximab. 

Overall, the study suggests that the systemic manifestations of TNF-α inhibitors-induced SLE range from mild to rare and life-threatening, including skin involvement, arthritis, pleuritis, pericarditis, and renal impairment.

The authors concluded thta further research is necessary to validate their findings.