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A retrospective analysis shows patients unresponsive to either secukinumab, ixekizumab or brodalumab may benefit from another of them.
Interclass switching among interleukin 17 (IL-17) inhibitors may be a safe and effective strategy for patients with psoriasis, according to new data.1
In research from a team of Italy investigators, patients with moderate to severe psoriasis reported decreased Psoriasis Area Severity Index (PASI) scores by 16 weeks, followed by maintained treatment response through 52 weeks, when switching from one of secukinumab, ixekizumab or brodalumab to another.
The findings highlight a consistent benefit from the IL-17-targeting agents, which have become a more prominent option in the psoriasis drug class.
Led by Francesco Cavallo, of the department of medical sciences at the University of Turin, investigators conducted a retrospective analysis of medical chart data to from their university hospital to interpret impact of IL-17 intraclass switching among patients with moderate to severe psoriasis. As IL-17 and IL-23 targeting has become a representative “mainstay of the increased inflammatory response” observed in psoriasis treatment, agents like secukinumab, ixekizumab, and brodalumab have been individually proven to be highly efficacious and safe for patients.
“Unfortunately, a substantial proportion of patients shows a primary or secondary inefficacy to the treatment, as well as the onset of adverse events leading to discontinuation of the treatment,” investigators wrote. “In the abovementioned cases, the clinician can face the challenge of changing the therapeutical axis (swap) or keep maintaining the same axis by performing an intraclass switch.”
Though preliminary data from real-life practice shows a potential benefit in switching from one IL-17 to another in these circumstances, the topic remains broadly understood by practicing clinicians.
Cavallo and colleagues identified 648 patients receiving IL-17 inhibitors for moderate to severe psoriasis at their institution; of them, just 29 had undergone an intraclass treatment switch. No washout period nor intercurrent therapy regimen were implemented in any of these cases. Mean patient age was 55.1 years old at the time of switching, with a mean disease onset age of 28.8 years old; 13 (44.8%) patients were female.
Regarding comorbidities, 11 patients were obese per body mass index (BMI) scores >30; 13 had cardiovascular conditions; 4 were diabetic; and 26 suffered from psoriasis vulgaris. Another 16 had concomitant psoriatic arthritis.
Primary inefficiency of an IL-17 inhibitor was defined as nonresponse to treatment after 3-4 months; secondary inefficiency was defined as a loss of efficacy during treatment.
Investigators observed secukinumab being discontinued for either primary or secondary inefficiency in 19 cases; of them, 11 patients switched to brodalumab and 8 switched to ixekizumab. Among the 9 patients who discontinued ixekizumab, all switched to brodalumab. The 1 patient who discontinued brodalumab switched to secukinumab. Six (20.7%) patients discontinued therapy due to primary inefficiency, 21 (72.5%) discontinued due to secondary inefficiency, and 2 (7.0%) discontinued due to onset of adverse events.
Mean PASI score was 11.1 at the time of intraclass switches; the mean score dropped to 5.2 afterward. Investigators noted 9 (31%) patients actually achieved full skin clearance per PASI 100 at week 16 of their switched regimen. Mean PASI was 3.4 at week 28, then 3.0 at week 52.
There were no statistically significant differences between mean PASI drop among patients with or without biologic treatment history who switched IL-17 agents due to primary or second inefficiencies. After a median follow-up time of 18.7 months post-switch treatment, all but 2 patients had been continuing treatment.
Highlighting the unique targeting capabilities and affinities with the IL-17 pathway associated with each of the 3 observed agents, Cavallo and colleagues concluded the benefit of intraclass switching for psoriasis may be explained by potentially unknown mechanism that could be interpreted by clinical and molecular assessments alike.
“Further studies will be needed on a larger patient population; however, our data, together with the available data in the literature, clearly confirm that intraclass switching among IL-17 inhibitors may be a safe and effective therapeutic option for patients who show inefficacy from the first IL-17 inhibitors line,” they concluded.