Systematic review of anti-drug antibodies of IL-17 inhibitors for psoriasis

Three main biologics target the IL-17 pathway; these include secukinumab, ixekizumab, brodalumab, all of which are approved for treatment of moderate-to-severe plaque psoriasis. We performed a systematic review of the literature to determine if IL-17 inhibitors are prone to develop anti-drug antibodies (ADA) and how efficacy of treatment is influenced. A total of 14 papers were reviewed. Only one secukinumab trial detected treatment-emergent ADA in 4 out of 996 (0.41%) patients during the 52-week treatment period. Two of these patients (1 on 150-mg retreatment as needed and 1 on 150-mg fixed interval) were found to have neutralizing antibodies; however, they were not associated with decreased efficacy. One paper reported ADAs against ixekizumab. One out of 1150 (9%) developed titers to ixekizumab after receiving 160-mg-loading dose followed by 80 mg every 2 weeks. Nineteen out of 1150 (1.7%) developed high titer (>1:1280) which impacted clinical outcomes. Three studies did detect ADA against brodalumab; however, none were neutralizing. It is difficult to draw a conclusion from our findings given the variability in ADA development. Most trials did not develop ADA, and if they did, the majority of the time they were not neutralizing. Only ixekizumab showed decreased efficacy, but no increased adverse events in cases with neutralizing ADA.