Xeljanz, the FDA, and nine years of patient harm

Quantifying population-level adverse events in the near decade between when safety concerns were identified and FDA action
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Originally published on 05/31/2022 in Drug Pricing Lab

Regulatory delays in the face of pressing safety concerns

Since its initial approval in 2012, safety concerns regarding increased risk of malignancy, serious infection, and cardiovascular events have followed Pfizer's blockbuster rheumatoid arthritis drug Xeljanz. Combining the FDA’s originally generous timeline of 5 years to conduct a post-marketing safety study with a series of delays in the study design, completion, reporting, and FDA action, nearly a decade passed before Xeljanz’s boxed warning was updated and expanded to include an increased risk of death.

The Drug Pricing Lab utilized the attributable risk calculation, a common epidemiological tool, to quantify the cumulative excess harm suffered by people treated with Xeljanz during this period. Approximately 897 additional individuals were diagnosed with a malignancy due to receiving Xeljanz rather than another equally effective treatment. In addition, about 436 people died unnecessarily, 466 experienced avoidable major adverse cardiovascular events, and 429 experienced other types of cardiovascular events.

Read the full report here.

Cumulative excess patient harms, Xeljanz vs TNFi, November 6, 2012 – December 2, 2021

Key events:

FDA approvals for Xeljanz:

A1: rheumatoid arthritis, November 2012
A2: psoriatic arthritis, December 2017
A3: ulcerative colitis, May 2018
A4: juvenile idiopathic arthritis, September 2020

R: REMS requirement dropped, February 2016
W: Weighted average time for safety signals to emerge from pre-approval studies, 11.6 months

Note: The malignancies category excludes non-melanoma skin cancers. The major adverse cardiovascular events (MACE) category includes cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke of any classification.


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