A recent review reveals older adults are underrepresented in trials investigating systemic immunomodulators as a treatment for atopic dermatitis.
The lack of older adults in trials of systemic immunomodulators for atopic dermatitis (AD) means that available evidence may not be safely generalizable to these patients, according to a recent review.
“Both psoriasis and atopic dermatitis are common in older adults. And older adults in general are more at risk for adverse events from medications. We need to know how effective and safe medications for psoriasis and atopic dermatitis are in this population,” says lead study author Aaron Drucker, M.D., ScM. Dr. Drucker is a clinician scientist in the Division of Dermatology at Women’s College Hospital and Women’s College Research Institute and assistant professor in the Department of Medicine at the University of Toronto.
Age-related changes in drug metabolism, as well as the likelihood of increased comorbidities and polypharmacy, make older patients more susceptible to drug-related adverse events, study authors write. For example, methotrexate is considered less safe in this population due to reduced renal clearance. Similarly, cyclosporine is contraindicated in patients with renal impairment, uncontrolled hypertension or relevant malignancies; cyclosporine also interacts with many common medications.
Research from the United States and the United Kingdom suggests that the prevalence of AD in people over 65 years old is approximately 7%. Yet according to the review, published online Aug. 19, 2020 in JAMA Dermatology, none of the trials analyzed reported separate efficacy or safety outcomes for older adults.
Investigators searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE and clinicaltrials.gov through Nov. 7, 2019. Ultimately, 32 trials including 4547 participants total met inclusion criteria.
Of these 32 trials, 11 (most involving cyclosporine) reported explicit upper age limits ranging from 42 to 70 years. Although seven of 12 dupilumab (Dupixent, Sanofi and Regeneron) trials lacked upper age limits, only 67 of 1472 total participants (4%) were over age 65; the gender of older participants was not reported. Overall, 10 trials included at least one participant age 65 or older.
More than two-thirds of the studies reviewed used eligibility criteria that may have disproportionately excluded older patients. The most frequent examples of such criteria included history or presence of malignant neoplasms (56%), uncontrolled hypertension (28%), renal or pelvic dysfunction (25%), use of drugs likely to interfere with study drugs’ pharmacokinetics (22%) and abnormal laboratory values (19%).
The situation in AD is not unique, authors add, as stringent criteria of clinical trials in many diseases may indirectly exclude older adults. The widely used major diagnostic criterion of flexural dermatitis may represent another obstacle because flexural dermatitis occurs less commonly in older adults than in younger adults and children.
Dr. Drucker says he hopes that the study’s findings bring awareness to the dearth of data regarding older adults in studies of systemic AD drugs. “When we pick treatments and counsel our patients on these drugs,” he says. “that should be part of the discussion. We have to do the best with the data we have, which in a way means flying blind. We have to use data from younger people and understand that it’s uncertain whether these data apply to older people.”
To help clarify the safety and efficacy of systemic AD treatments for older patients, Dr. Drucker and colleagues suggest conducting observational studies. While randomized clinical trials are the ideal study design, Dr. Drucker notes, such trials are expensive, resource-intensive and unlikely to occur for drugs already approved.
“Observational studies can be done with fewer resources and can provide very helpful data in more generalizable populations outside of clinical trials,” he says. Future trials also could increase participation of older adults by reducing comorbidity-related exclusion criteria, eliminating age-related exclusion criteria and setting specific recruitment targets for older adults.”
1. Lam M, Zhu JW, Maqbool T, et al. Inclusion of older adults in randomized clinical trials for systemic medications for atopic dermatitis: a systematic review [published online ahead of print Aug 19, 2020]. JAMA Dermatol. 2020;10.1001/jamadermatol.2020.2940. doi:10.1001/jamadermatol.2020.2940
Dr. Drucker has received institutional research funding from Sanofi and Regeneron. He has been a consultant for Sanofi and RTI Health Solutions, and his institution has received educational grants from Sanofi and Regeneron.