Does Early Intervention Promote Favorable, Sustained Outcomes in Psoriasis?

The impact of early intervention in psoriasis will soon be more clear, say researchers of a new study, highlighting initial indications that early intervention may offer more favorable long-term prognosis for patients.

The exploration of whether early intervention has an impact in psoriasis follows data from other immune-mediated diseases in which evidence is mounting for the benefits of intervening early on in disease duration. Interest has also been paid to disease memory in psoriasis, as molecular and cellular changes may persist even in resolved psoriatic lesions.

“The benefits of early therapeutic intervention have been demonstrated in several immune‐mediated diseases, although the evidence of early intervention and disease memory in psoriasis is sparse and inconsistent,” described the researchers in Journal of the European Academy of Dermatology & Venereology. “The literature is characterized by observational studies and post hoc analyses of randomized controlled trials [RCTs] that are not optimally designed to test this hypothesis. However, an early intervention within 2 years of disease onset may provide a more favorable long‐term prognosis in plaque psoriasis.”

Two ongoing studies may soon offer more insight into the impact of early intervention with biologics in patients with short disease duration, noted the researchers, citing the STEPin study of patients with new-onset psoriasis and the GUIDE study of patients with a short disease duration.

The GUIDE study of 850 patients is investigating whether guselkumab leads to improved and sustained responses in those who got their diagnosis 2 or fewer years ago compared with patients who have known of their diagnosis for over 2 years. Interim data from the study show that even when addressing multiple factors, the group of patients with shorter disease duration were more likely to achieve disease clearance at weeks 20 and 28.

The STEPin study will determine whether early intervention with secukinumab yields improved responses at week 52 that are sustained through week 208 compared with narrowband ultraviolet light B phototherapy among 160 patients.

As data are awaited from the 2 clinical trials, current data on early intervention are limited to prospective studies and post hoc analyses, including a post hoc analysis of over 1100 patients from the ReSURFACE 1 and 2 RCTs. They found that among patients treated with tildrakizumab for 28 weeks, the mean duration of psoriasis was 21.18, 17.98, 18.21, 17.09, and 14.87 years for patients who achieved psoriasis area and severity index (PASI) less than 50, PASI 50-74, PASI 75-89, PASI 90-99, and PASI 100, respectively.

Results from a recent prospective study of 700 patients with new-onset disease followed for 10 years showed that at the 10-year check in, patients who began systemic treatment at or before enrollment in the study were less likely to have severe disease than those who began treatment after enrollment: 38% vs 65%.

“The results from the observational studies and post hoc analysis should be interpreted with caution due to the limitations of their design. Despite statistical adjustments, both known and unknown factors may confound the associations and therefore the causality of early intervention and improved clinical outcomes cannot be concluded,” commented the researchers. “Moreover, it is unknown whether patients with short compared to long disease duration have more favorable long‐term outcomes due to disease memory modification by treatment or simply due to the inclusion of patients with a tendency to remission by natural course irrespective of treatment.”

The researchers explained that rationale for systemic treatments affecting disease memory stems from T cells that may remain in the skin as effector-memory-resident cells following treatment. For example, CD8+ cells, prevalent in the epidermis of psoriasis skin, are often tissue-resident memory T cells and persist despite treatment, suggesting they could be leveraged as potential biomarkers for deep, long-term remission and residual disease.

Reference

Abdallah H, Emmanuel T, Bregnhøj A, Johansen C, Iversen L. Early intervention and disease memory in psoriasis: a literature review. JEACV Clin Practi. Published online September 27, 2022. doi:10.1002/jvc2.63