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No Incremental Safety Risk Attributable to Anti-TNF Therapy in Older Patients with Ulcerative Colitis

Key findings

  • In this analysis, researchers pooled patient-level data from four multicenter, randomized, double-blind, controlled trials of tumor necrosis factor-a antagonist (anti-TNF) therapy in patients with moderate to severe ulcerative colitis
  • There was no incremental risk of serious adverse events or hospitalization attributable to anti-TNF therapy in 231 older patients (≥60 years of age) compared with 2,026 younger patients receiving infliximab or golimumab
  • There were no statistically significant differences in the rates of severe or non-severe infections among older patients receiving anti-TNF therapy compared with those on placebo
  • Treatment with anti-TNF had similar efficacy on clinical remission after induction and maintenance therapy in older and younger patients

Multiple studies have noted that older patients with moderate to severe ulcerative colitis (UC) are less likely than younger patients to receive anti–tumor necrosis factor-α (anti-TNF) agents, even though they're among the most effective medications for induction and maintenance of remission.

An important explanation may be the perception of increased treatment-related risks, especially for patients who take numerous other medications. Previous research has indicated that older patients on biologic therapies have significantly higher rates of complications than younger patients, including higher rates of serious infections. However, these studies have mostly relied on observational data, possibly without a placebo control group to assess background levels of risk without treatment.

To isolate the effect of age on serious adverse events, David Cheng, PhD, instructor in investigation at the Mass General Biostatistics Center, Kelly C. Cushing, MD, former clinical research fellow with the Department of MedicineAshwin N. Ananthakrishnan, MD, MPH, director of the Crohn's and Colitis Center, and colleagues pooled individual patient-level data from four randomized, controlled clinical trials of anti-TNF agents in UC. In Clinical Gastroenterology and Hepatologythey present robust evidence of the comparative safety and efficacy of anti-TNF therapy for older patients.

Study Methods

The researchers examined data from the Active Ulcerative Colitis (ACT) Trials 1 and 2 of infliximab and the PURSUIT-SC and PURSUIT-Maintenance trials of golimumab. The study cohort included 2,257 patients with UC, of whom 231 (10%) were older (defined as ≥60 years of age). The average ages of the older and younger groups were 65 and 38, respectively.

The primary outcome was any serious adverse event (SAE) classified as "severe" in intensity by trial investigators. SAEs were defined as death, life-threatening event, hospitalization or significant disability. Clinical remission was defined based on achievement of a Mayo score ≤2 with no subscore >1 after induction and maintenance therapy.

Data were pooled and analyzed using multivariable logistic regression adjusting for demographics and baseline concomitant therapies (immunomodulators and corticosteroids) and random effects to account for between-trial differences.


Compared with younger adults, older patients had significantly higher rates of SAEs and hospitalizations. However, older patients on placebo also had higher rates of SAEs and hospitalizations. Taking this into account in multivariable analysis, there was no incremental risk attributable to anti-TNF among older patients. Rates of severe and non-severe infections as well as neoplasms were similar not statistically different across patient groups, though the rarity of neoplasms made it difficult to detect any differences.


Older patients had similar rates of clinical remission relative to younger patients after both induction and maintenance therapy with anti-TNFs in multivariate analyses. When accounting for background placebo rates, the efficacy of anti-TNF agents remained similar in older vs. younger patients after induction and maintenance therapies.

No Incremental Risk Attributable to Anti-TNF Therapy

In this study, differences in the observed rates of SAEs between older and younger patients receiving anti-TNFs appear to have been driven by differences in baseline risk rather than true safety signals related to treatment. As a result, withholding effective biologic therapy may still lead to differences in adverse events due to inherent differences in baseline risks.

Nevertheless, neoplasms were observed among multiple patients treated with anti-TNFs on average after 85 weeks (1.6 years) following initiating treatment. This suggests the need for continued long-term clinical monitoring of patients receiving anti-TNFs.

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