Systemic psoriasis therapies not age-dependent

Although data regarding systemic psoriasis medications in older patients are limited, this does not necessarily mean dermatologists should avoid prescribing these therapies in this age group, according to authors of a recent review1. However, they add, these decisions require careful consideration, and these patients may require more frequent follow-up.

“As the world population is rapidly aging, and psoriasis is a chronic disease, older adults with psoriasis frequently present at the dermatology outpatient clinic,” says corresponding author Marieke E. C. van Winden, M.D. She is a Ph.D. candidate in dermatology at Radboud University Medical Centre in Nijmegen, the Netherlands.

Several studies have shown that disease characteristics and severity in older adults are highly comparable with those seen in younger patients, says van Winden. Therefore, she says, systemic treatment could be indicated for older patients, if aligning with their preferences, as frequently as for younger patients.

“However, it can be challenging to treat the older patient population appropriately due to comorbidities, co-medication, organ impairment, functional deterioration and frailty. To provide more guidance for physicians treating this growing group of patients, specific research in the geriatric population is needed.”

In November 2019, researchers led by principal investigator Satish F. K. Lubeek, M.D., Ph.D., systematically searched Embase, MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies reporting efficacy or effectiveness and safety findings in patients age 65 years or older.

Ultimately, 31 articles including 39,561 patients met inclusion criteria for the review, which appeared online August 19 in JAMA Dermatology. Included studies, in particular those on conventional systemic therapy, were heterogenous regarding age cutoffs, treatment regimens and methodological approaches.

Regarding efficacy, authors say the effectiveness of acitretin, etanercept, adalimumab and secukinumab does not seem age-dependent. At weeks 12 through 16 of treatment, the proportions of patients reaching Psoriasis Area and Severity Index (PASI) 75 with these medications ranged from 27% to 47.8%, 15.6% to 64%, 60.7% to 65%, and 86.4%, respectively.

Studies regarding other systemic medications lacked age-group comparisons. At 12 to 16 weeks, 49% of older methotrexate users reached PASI 75, as did 46% to 52.6% of older cyclosporine users, 66.7% to 93% of older infliximab users and 56.5% of older ustekinumab users. The only drugs for which investigators found long-term (52-week) results were etanercept, adalimumab, ustekinumab and secukinumab, which achieved PASI 75 in 60% to 86.4% of older patients.

Most systemic therapies showed no significant association between adverse events (AEs) and age. However, older age was significantly associated with safety issues including impaired renal function in cyclosporine users (33%, versus 9% of younger patients; P=0.03). Additionally, cyclosporine use in patients 65 years or older was associated with a significantly higher overall AE rate (1.4 per patient-year/PY) versus methotrexate (0.12 per PY; P<0.001). In a fumaric acid esters study, development of T cell lymphopenia was significantly associated with older age (hazard ratio: 2.42).

Van Winden says it is unclear whether the dearth of geriatric data for systemic psoriasis therapies is contributing to undertreatment (in case drugs’ safety profiles are better than anticipated) or exposing older patients to avoidable risks. “The studies included in our systematic review mostly show comparable effectiveness and safety between both age groups, although reversible adverse events of cyclosporine and fumaric acid esters were associated with older age.” Other important AEs of conventional systemic agents in older patients included liver dysfunction with methotrexate and hypertension with cyclosporine.

Patient age in itself should not dissuade dermatologists from prescribing systemic psoriasis therapies, authors conclude. However, older age can signal dermatologists to evaluate patient- and aging-related factors and/or arrange more frequent assessments if needed, adds van Winden. “Moreover, this patient population is highly heterogenous, and individual treatment goals and preferences should be assessed in order to improve shared decision-making and avoid under- and over-treatment,” she says.

Disclosure:

Dr. van Winden has performed investigator-initiated research with financial support from Almirall SA and is performing clinical trials for AbbVie, Celgene Corporation, Janssen Pharmaceuticals, Leo Pharma A/S, Eli Lilly and Company, and Novartis International AG.

References:

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 [Published online ahead of print August 19, 2020]. JAMA Dermatol. 2020 Aug 19. doi: 10.1001/jamadermatol.2020.2311.