Many Immunosuppressive Medications Safe for Elderly Patients With Inflammatory Bowel Disease

Digestive Disease Week (DDW) 2014

May 3-6, 2014; Chicago, IL

As the US population continues to age, elderly patients are representing an increasing proportion of the patient population with inflammatory bowel disease (IBD). It has been reported that approximately 10% to 30% of the IBD population is older than 60 years, with 10% to 15% of all new IBD cases being diagnosed in this age group. Patients with IBD often require immunosuppressive medications to manage their IBD; however, there is a paucity of data regarding the safety of these medications for elderly patients with IBD. During the DDW meeting, Jason K. Hou, MD, assistant professor of medicine, Baylor College of Medicine, Houston, TX, and colleagues reported the results of their cross-sectional study, which indicated that many immunosuppressive medications appear to be safe for elderly patients with IBD, though more long-term studies are needed.

Hou and colleagues’ study included 144 older adults (≥65 years; mean age, 71.6 years) with IBD, whether Crohn’s disease (57%), ulcerative colitis (38%), or unclassified disease (5%), who received care at the Baylor College of Medicine from July 2009 to June 2013. Patients were categorized according to the IBD medications they were exposed to, which included aminosalicylates/sulfasalazine, methotrexate, systemic steroids (prednisone, methylprednisolone), thiopurines (azathioprine, 6-mercaptopurine), and biologics (infliximab, adalimumab, and certolizumab pegol). The investigators then assessed for a variety of potential medication-related complications, including infections, leukopenia, pancreatitis, hepatitis, osteoporosis/osteopenia, and cancer. The study’s primary end point was association of medication exposure with the composite end point of any medication-related complication, as identified using univariate and multivariate logistic regression.

Among the study patients, 46 (32%) were observed to have at least one complication. Using univariate analyses, exposure to thiopurines was associated with increased odds of any medication-related complication (odds ratio [OR], 3.23; 95% confidence interval [CI], 1.53-6.80). When examining specific complications, patients exposed to thiopurines were more likely to experience infections (OR, 2.89; 95% CI, 1.08-7.76), but not other complications. This association remained significant on multivariate analyses that adjusted for sex, race, disease duration, and smoking history (OR, 4.21; 95% CI, 1.84-9.65). None of the other examined medications, including biologics, were associated with immediate medication-related complications.

Based on their findings, Hou and colleagues conclude that thiopurine use in elderly patients with IBD requires close monitoring for infectious complications, as it increased the risk of complications 3-fold compared with all other medication exposures, including biologics. Annals of Long-Term Care: Clinical Care and Aging^® (ALTC) had the opportunity to discuss this study in greater detail with Hou.

ALTC:  In your study, you assessed patients’ exposures to different immunosuppressive agents used to treat IBD. What constituted an exposure (eg, was any exposure considered, or were patients only classified as having an exposure if they were on an agent for a specified amount of time)?

Hou: We included patients who were exposed to any amount of a specific medication. Because of our relatively small sample size, we were unable to analyze based on duration of exposure. As the most common complications observed were infections, these may occur with relatively short exposure to immunosuppressive medications.

What determined if patients had exposures to several of the assessed medications? How were potential complications attributed in such cases?

All medication exposures and complications were confirmed using a chart review.  We did adjust for exposure to other IBD-related mediations. In cases where patients were concurrently on multiple medications at the time of a complication, each was listed as possibly related to the complication.

Elderly patients have a high prevalence of comorbidities and polypharmacy.  Was this accounted for in your analyses?

We adjusted for concomitant use of other IBD medications, but not for other, non-IBD medications. We focused our analyses on complications that have been previously reported with IBD-related medications.

Why do you think the risk of infections was so much greater with thiopurines compared with the other immunosuppressive agents? Do you think similar results would be observed in younger patients?

We were somewhat surprised that thiopurines were associated with a higher risk of infection while prednisone was not. This may be in part related to the short time patients are exposed to prednisone in our practice compared with the long-term use of thiopurines. We found it interesting that tumor necrosis factor-alpha antagonists were not associated with an increased risk of infection. I am concerned that thiopurines will also increase the risk of infection among young patients; however, the difference may not be as pronounced as we observed in older patients.

Were any particular types of infections more common in patients experiencing this complication following thiopurine use?

We considered an infectious complication as one that required a prescription for an antibiotic or cessation of medications. We did not observe a predominance of any one particular infection with thiopurine use.

There have been some concerns over the use of various biologics, but your study did not show them to be associated with any increased risks of medication-related complications among your study population. Do you think healthcare providers treating elderly persons should feel more secure prescribing these agents, and is there anything they should keep in mind when prescribing these agents?

Our study demonstrated that biologics are not strongly related to infectious complications among elderly patients with IBD. However, a prior study did show an increased risk of mortality related to biologics in a similar population. Both our studies were retrospective, so further studies are still needed to fully understand the risks involved with biologics among elderly patients. Use of any immunosuppressive medication in the elderly population requires an in-depth discussion with the patient and consideration of comorbidities, but our data suggest biologics have a lower risk of infectious complications compared with thiopurines.—Christina T. Loguidice