Friday, 14 Dec 2018

You are here

Thiopurines and Anti-TNF drugs in IBD Associated with Increased Lymphoma Risk

JAMA presents a French report on the cancer risk of thiopurine or tumor necrosis factor inhibitor (TNFi) use in adult patients with inflammatory bowel disease (IBD) and finds a raised risk for lymphoma in IBD compared to those not treated with these agents.  (Citation source https://buff.ly/2z04f9h)

Using national French National Health Insurance databases, they studied adults with IBD between 2009-2013, with follow-up through 2015; specifically looking for lymphomas associated with thiopurines and anti-TNF agents.

The study included 189,289 patients (median age 43 years) with a medial follow up of 6.7 years. Cohorts included those never exposed (n 123 069), thiopurine monotherapy exposed (n 50405), TNFi exposed (30294), and combination therapy exposed (14229).

For those drug exposed, there were a total of 336 lymphomas and the incidence rate was 0.26 per 1000 person-years (95% CI, 0.23-0.29), The drug-related risks were:

  • thiopurine monotherapy - adjusted hazard ratio [aHR] = 2.60; 95% CI, 1.96-3.44 (P < .001)
  • anti-TNF monotherapy - aHR = 2.41; 95% CI, 1.60-3.64 (P < .001)
  • combination therapy - aHR = 6.11; 95% CI, 3.46-10.8 (P < .001).

Lymphoma subtypes included nonfollicular lymphoma (130 cases, 39%), diffuse large B-cell lymphoma (83 cases); Hodgkin lymphoma (55 cases, 16%); and follicular lymphoma (41, 12%). Hodgkin lymphoma made up 14% of all lymphomas among unexposed patients, 19% among patients exposed to thiopurines, 19% in those exposed to TNF blockers, and 43% in those exposed to combination therapy.

Editor's note: these findings are in line with what has been reported for TNFi previously by the FDA and is reflected in the product label for each TNFi. What is unique here is that in patients with rheumatoid arthritis, the rate of lymphoma was higher (2-6 fold higher) when comparing patients on drug to those in the normal population; but was equal to other RA patients not taking TNFi.  These studies show that in IBD the lymphoma risk was roughly 2.5 fold higher when comparing IBD patient on TNFi or thiopurine to those not taking these aggressive therapies.  While this most likely represents the channeling bias of those with more aggressive disease receiving more aggressive therapy. The authors noted that the benefits of these agents in IBD must be weighed against the absolute risk of < 1 lymphoma per 1000 patient-years of exposure.

In IBD patients the use of thiopurine monotherapy or anti-TNF monotherapy was associated with a small but statistically significant increased risk of lymphoma compared with exposure to neither medication, and this risk was higher with combination therapy than with each of these treatments used alone. 

Disclosures: 
The author has received compensation as an advisor or consultant on this subject

Add new comment

More Like This

CDC Top 15 Most Common Opioid Overdose Drugs

The Dec. 12 issue of the National Vital Statistics Reports from the U.S. Centers for Disease Control and Prevention reports that the most commonly abused drugs causing drug overdose deaths (between 2011-2016) include fentanyl, heroin, oxycodone, and cocaine.

Trazodone High Risk of Falls and Fractures

The CMAJ (Canadian Medical Association Journal) has reported that trazadone use in the elderly may be associated with a risk of falls and major fractures. 

Using claims data from ICES, researchers compared 6588 seniors given trazadone to 2875 receiving another atypical antipsychotic.

Musculoskeletal Events with Statin Use

Analysis of the FDA Adverse Event Reporting System data examined the association between statins' musculoskeletal adverse events (MAEs).

Review of the data shows that atorvastatin and rosuvastatin (with strong low‐density lipoprotein cholesterol‐lowering effects) had a higher risk and a faster onset of MAEs when compared with simvastatin.

They could not detect whether concomitant drugs shifted the onset timing of MAEs. 

Low Short-Term Risks of NSAIDs in High Risk Patients

JAMA has published a large Canadian claims-based study showing that nonsteroidal anti-inflammatory drug (NSAID) use in patients with hypertension, heart failure, or chronic kidney disease was not associated with a significant safety risk - but this only looked at short-term outcomes (7-37 days of exposure). 

Update on Checkpoint Inhibitor Safety

“Autoimmunity is the Achilles heel of onco-immunotherapy” per Dr. Leonard Calabrese, which leaves a dilemma for rheumatologists. Onco-immunotherapy induces immune dysregulation to allow patients to develop an immune response to their cancer cells. An unfortunate side effect for patients taking onco-immunotherapy is often autoimmune-like diseases referred to as immune adverse reactions (irAEs). Studies in France and the United States have shown that irAEs can be a good prognostic sign, suggesting these therapies are working. Rheumatology is faced with new problems as onco-immunotherapies may induce new chronic diseases in multiple different forms secondary to the treatment.