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Challenges of Treating Older Patients With Systemic Therapies

There are many unique challenges to treating older patients with either psoriasis or atopic dermatitis (AD). Comorbidities, such as cardiovascular disease, concomitant medication use, decreases in physiological functions, such as renal function, and increases in the risk for adverse effects associated with therapies can impact treatment decisions and outcomes.

Two systemic reviews published in JAMA Dermatology examined the use of immunomodulatory therapies among older adults with psoriasis and AD.1,2 Both reviews highlight what Daniel Butler, MD, in his accompanying editorial describes as “the limitation of dermatology’s current understanding and research infrastructure for common diseases in older adults.”3 In one systemic review, van Winden et al1 evaluated the efficacy and safety of systemic psoriasis therapies among adults aged 65 years or older. The second systemic review by Lam et al2 examined the representation of older adults in randomized clinical trials that assessed the safety and efficacy of systemic immunomodulatory treatments for AD.

van Winden et al1

Using Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL), van Winden et al searched for randomized clinical trials, cohort studies, large case series, and meta-analyses that had assessed the efficacy and safety of systemic therapies among patients with psoriasis aged 65 years or older. Their final analysis included 31 articles with a total of 39,561 patients. Overall, there were limited data available per systemic agent, and the overall quality of the included studies was low.

Among oral therapies, van Winden et al found that a reduction of 75% in Psoriasis Area and Severity Index (PASI 75) had been achieved after 12 to 16 weeks of treatment in 49% of 74 patients treated with methotrexate sodium, 46% to 52.6% of 178 patients treated with cyclosporin, and 27% to 47.8% of 108 patients treated with acitretin. After 12 to 16 weeks of treatment with biologics, PASI 75 was achieved in 15.6% to 64% of 256 patients treated with etanercept, 66.7% to 93% of 43 patients treated with infliximab, 60.7% to 65% of 100 patients treated with adalimumab, 56.5% of 46 patients treated with ustekinumab, and 86.4% of 67 patients treated with secukinumab.

In addition, they found that the effectiveness of acitretin, etanercept, adalimumab, and secukinumab did not appear to be associated with age. However, age group comparisons were not provided for other systemic therapies.

They also found older age was significantly associated with renal function deterioration among patients treated with cyclosporine, and with lymphopenia among those treated with fumaric acid esters (hazard ratio, 2.42; 95% CI, 1.65-3.55). The most frequently reported adverse event among biologic-treated patients aged 65 years or older was infection, but the researchers did not find any significant association with age.

Lam et al2

Lam et al searched for randomized clinical trials that included safety and efficacy data of systemic immunomodulatory treatments of AD among older patients using CENTRAL, Embase, and MEDLINE databases, as well as the trial register. They analyzed 32 trials with a total of 4547 participants (mean age 34.4 years).

Overall, Lam et al found 11 trials (34%) reported an explicit upper age limit ranging from 42 to 70 years of age. In addition, they observed 25 trials (69%) had other exclusion criteria that would disproportionately exclude older adults. Only 10 trials (31%) were found to include adults aged 65 years or older.

A total of 9 trials had examined the safety and effectiveness of cyclosporine. In 7 trials that evaluated dupilumab and included a proportion of older participants, only 112 (4%) of 2964 participants were aged 65 years or older. In addition, they found none of the trials stratified safety or efficacy data for older adults.

Future Research

For psoriatic diseases, more real-world evidence and subanalyses of prospective cohort studies on the effectiveness and safety of systemic treatments among older adults are needed to optimize the management of this skin disease in older patients, said van Winden et al.1

Lam et al2 also stressed the importance of including older patients with atopic dermatitis in randomized clinical trials and observational studies to address the gap in safety and efficacy data for this patient population.


The underrepresentation of older adults in randomized clinical trials means clinicians and patients lack evidence to support safe, evidence-based treatment decisions for patients aged 65 years and older. “Without true representation in research practices, clinicians and patients are left to struggle with clinical decisions,” wrote Dr Butler.3

Lam et al2 stated that clinicians and patients should be aware of this evidence gap when selecting a systemic treatment option for atopic dermatitis. While there is limited evidence on the safety and efficacy of systemic psoriasis therapies for this patient population, van Winden et al noted that “age alone should not be a limiting factor in psoriasis management.”1


1. van Winden MEC, van der Schoot LS, van de L’Isle Arias M, et al. Effectiveness and safety of systemic therapy for psoriasis in older adults: a systematic review. JAMA Dermatol. Published online August 19, 2020. doi:10.1001/jamadermatol.2020.2311

2. 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. JAMA Dermatol. Published online August 19, 2020. doi:10.1001/jamadermatol.2020.2940

3. Butler DC. Dermatology’s management of flagship diseases in older adults: lifting the blindfold. JAMA Dermatol. Published online August 19, 2020. doi:10.1001/jamadermatol.2020.2310

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