New research provides compelling evidence that biologic therapies targeting interleukin (IL)-17 and IL-23 offer both safety and efficacy advantages for elderly patients with psoriatic disease, potentially changing treatment approaches for this vulnerable population.
Comparable Long-Term Efficacy Despite Initial Response Differences
A retrospective analysis of 121 patients with moderate-to-severe plaque psoriasis treated with IL-17 or IL-23 inhibitors (secukinumab, ixekizumab, guselkumab, or risankizumab) revealed important age-related response patterns. The study divided patients into two groups: those younger than 65 years (n = 78) and those 65 or older (n = 43).
At the early 12/16-week assessment, younger patients demonstrated significantly higher response rates across all Psoriasis Area and Severity Index (PASI) measures. PASI75 was achieved by 90.5% of younger patients compared to 65.1% of older patients (p = 0.010), with PASI90 rates showing similar disparities (75.7% vs. 32.6%, p = 0.030).
However, these differences largely disappeared by Week 52, with elderly patients showing PASI75 and PASI90 rates approaching those of younger patients (97.5% vs. 86.3%, p = 0.055; 90% vs. 78%, p = 0.112, respectively).
"These findings suggest that while elderly patients with psoriasis may experience a delayed early response, long-term treatment with IL-17 and IL-23 inhibitors remains highly effective and durable," noted the study authors from Zangrilli et al. in JAMA Dermatology.
Drug survival rates remained impressively high across both age groups, with 79.6% of younger patients and 90.3% of older patients maintaining therapy at 24 months (log-rank p = 0.407). No significant differences emerged between IL-17 and IL-23 inhibitors in either age group regarding drug survival or PASI outcomes.
Reduced Infection Risk in Elderly Patients
A separate population-based cohort study published in JAMA Dermatology examined infection risks associated with different systemic psoriasis treatments in older adults. The study analyzed data from 11,641 older adults (median age 71 years) with psoriatic disease in Ontario, Canada, who initiated systemic therapy between 2002 and 2020.
During a median follow-up period of 4.8 years, 1,967 serious infections requiring hospitalization were reported. The incidence rates of serious infections per 100 person-years varied significantly by treatment:
- Methotrexate: 2.7
- Other older systemic medications: 2.5
- Anti-TNF biologics: 2.2
- IL-12, IL-23, or IL-17 inhibitors: 1.4
- Tofacitinib: 8.9
In multivariable-adjusted analysis, biologics targeting IL-12, IL-23, and IL-17 were associated with a significantly lower infection risk (Relative Rate 0.65; 95% CI, 0.48-0.88) compared to other treatments. Conversely, tofacitinib was linked to a significantly higher infection risk (RR 2.89; 95% CI, 1.14-7.34).
"The results of this study, combined with the established efficacy of biologics for psoriasis, suggest that biologics targeting IL-12, IL-23, and IL-17 could be favored over other agents to treat older adults," the researchers concluded.
Clinical Implications for Elderly Patient Management
These findings address a critical gap in psoriasis treatment knowledge. Around 15% of older adults with psoriasis experience moderate to severe disease, often necessitating systemic therapies for effective management. However, treatments considered low-risk in younger patients may pose greater toxicity concerns for older individuals.
The predictors of treatment discontinuation identified in the first study included female sex (HR 0.23, p = 0.005) and higher baseline PASI scores (HR 1.093 per point, p = 0.013), whereas age, biologic class, BMI, and prior biologic use were not significant factors.
Dr. Aaron Drucker, lead author of the infection risk study, emphasized the importance of these findings: "To inform treatment decisions for older adults with psoriatic disease, among whom infectious adverse events are a major concern, estimates of the relative risk of infection associated with different systemic treatments are needed."
Limitations and Future Directions
Both studies acknowledged certain limitations. The infection risk study noted that healthy user bias might explain some of the protective effects observed with newer biologics. Additionally, since Ontario Drug Benefit policies require older systemic medication use before biologics, direct comparisons between methotrexate and biologic users may not accurately reflect real-world clinical scenarios.
The efficacy study's retrospective design and relatively small sample size, particularly in the elderly cohort, may limit generalizability. However, the real-world nature of the data provides valuable insights beyond what controlled clinical trials typically offer.
Together, these studies provide reassurance to clinicians managing elderly patients with psoriatic disease, suggesting that newer biologic therapies targeting IL-17 and IL-23 pathways may offer an optimal balance of efficacy and safety in this vulnerable population.
