Composite Performance of Ixekizumab Impacted by Structural Damage, Functional Disability in Psoriatic Arthritis

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Low disease activity may be the most appropriate treatment target for patients with high levels of structural damage and functional disability.

Low disease activity (LDA) and remission were achieved in significant proportions of patients with psoriatic arthritis (PsA) treated with ixekizumab (Taltz, Eli Lilly), but there was variability in the performance of composite measures of PsA, according to a study published in RMD Open.1 Residual high patient-reported outcomes and functional disability were more common when assessed with the modified Composite Psoriatic Disease Activity Index (mCPDAI) and the Disease Activity index for Psoriatic Arthritis (DAPSA).

“Low disease activity may be the most appropriate treatment target for patients with high levels of structural damage and functional disability,” Laura C Coates, MBChB, MRCP, PhD, of the University of Oxford in the UK, and colleagues, stated. “Binary achievement of treatment targets assessed with any of the composite measures should not be used alone to inform treatment decisions.”

PsA can be evaluated by composite measures that assess disease activity and/or the achievement of treatment targets, including LDA and remission. In this study, the researchers evaluated the performance of ixekizumab, an interleukin-17A antibody, using data from 2 phase 3 randomized controlled trials, SPIRIT-P1 and SPIRIT-P2. The post-hoc analyses evaluated the effect of ixekizumab on achievement of LDA and remission with the minimal disease activity (MDA) and very low disease activity (VLDA) composite, DAPSA, Psoriatic Arthritis Disease Activity Score, GRAppa Composite ScorE, and mCPDAI. Residual symptom burden and the impact of structural damage and functional disability were quantified to assess performance.

Ixekizumab significantly reduced composite scores, and more patients achieved LDA and remission compared with placebo at week 24. Targets assessed by mCPDAI and DAPSA were achieved by more patients than other composites. While residual disease activity was similar between composites, residual high PROs and functional disability were more frequent when assessed with mCPDAI and DAPSA. Treatment target achievement was reduced in patients with high baseline levels of structural damage and functional disability with all composites, affecting MDA/VLDA most prominently.

Limitations to the study included that the data were from randomized clinical trials, so generalizing the results to a real-world population may be limited. Additionally, as these were descriptive analyses it is unclear if differences in proportions were statistically significant.

“In a multidimensional disease such as PsA, clinicians should assess all disease domains and functional and quality of life outcomes even if they are not included in the composite used,” investigators concluded. “This approach will enable identification of disease activity and functional disability from any cause (even though a treatment target is achieved) and avoid undertreatment. Clinicians can then tailor drug treatments and other interventions appropriately to ensure the best outcomes for patients.”


Coates LC, Smolen JS, Mease PJ, et alComparative performance of composite measures from two phase III clinical trials of ixekizumab in psoriatic arthritisRMD Open 2022;8:e002457. doi: 10.1136/rmdopen-2022-002457