Comparing Achievement of National Psoriasis Foundation Treatment Targets among Patients with Plaque Psoriasis Treated with Ixekizumab versus Other Biologics in Clinical and Real-World Studies

Abstract Introduction The National Psoriasis Foundation (NPF) recommends evaluating patient response to treatment at week 12, with a target response of ≤ 1% body surface area (BSA) affected by plaque psoriasis and an acceptable response of BSA ≤ 3% or ≥ 75% improvement. This post hoc analysis compared the achievement of NPF target and acceptable responses for ixekizumab (IXE) versus other biologics. Methods Outcomes were evaluated at week 12 for patients with moderate-to-severe plaque psoriasis from four head-to-head randomized clinical trials (RCTs; UNCOVER-2, UNCOVER-3, IXORA-R, and IXORA-S) and one real-world prospective observational study (Psoriasis Study of Health Outcomes; PSoHO). RCT patients were treated with IXE or etanercept (ETN; UNCOVER-2/3), guselkumab (GUS; IXORA-R), or ustekinumab (UST; IXORA-S). PSoHO patients were treated with anti-interleukin (IL)-17A biologics (IXE, secukinumab, SEC) and other approved biologics for the treatment of plaque psoriasis. Patients with missing outcomes were imputed as non-responder imputation. For RCT data, statistical comparisons between treatment groups were performed using Fisher’s exact test with no multiplicity adjustments. For real-world data, adjusted comparative analyses were performed using frequentist model averaging (FMA) and reported as odds ratio (OR). Results Across the four head-to-head clinical trials analyzed, significantly higher proportions of patients achieved target and acceptable responses at week 12 with IXE versus ETN, GUS, or UST. Likewise, the proportion of PSoHO patients achieving target and acceptable response at week 12 was higher with IXE compared with other individual biologics. Adjusted comparative analyses showed that IXE had significantly greater odds of target and acceptable response at week 12 versus SEC, GUS, risankizumab (RIS), adalimumab (ADA), UST, and tildrakizumab (TILD) and numerically greater odds of target and acceptable response at week 12 versus brodalumab (BROD). Conclusion Across both clinical studies and real-world settings, more patients treated with IXE achieved NPF target and acceptable responses at week 12 compared with those treated with other biologics. Trial Registration UNCOVER-2 (NCT01597245); UNCOVER-3 (NCT01646177); IXORA-R (NCT03573323); IXORA-S (NCT02561806); PSoHO (EUPAS24207)

Multifractality in fidelity sequences of optimized Toffoli gates

We analyze the multifractality in the fidelity sequences of several engineered Toffoli gates. Using quantum control methods, we consider several optimization problems whose global solutions realize the gate in a chain of three qubits with XY Heisenberg interaction. Applying a minimum number of control pulses assuring a fidelity above 99 % in the ideal case, we design stable gates that are less sensitive to variations in the interqubits couplings. The most stable gate has the fidelity above 91 % with variations about 0.1 %, for up to 10 % variation in the nominal couplings. We perturb the system by introducing a single source of 1 / f noise that affects all the couplings. In order to quantify the performance of the proposed optimized gates, we calculate the fidelity of a large set of optimized gates under prescribed levels of coupling perturbation. Then, we run multifractal analysis on the sequence of attained fidelities. This way, gate performance can be assessed beyond mere average results, since the chosen multifractality measure (the width of the multifractal spectrum) encapsulates into a single performance indicator the spread of fidelity values around the mean and the presence of outliers. The higher the value of the performance indicator the more concentrated around the mean the fidelity values are and rarer is the occurrence of outliers. The results of the multifractal analysis on the fidelity sequences demonstrate the effectiveness of the proposed optimized gate implementations, in the sense they are rendered less sensitive to variations in the interqubits coupling strengths.We analyze the multifractality in the fidelity sequences of several engineered Toffoli gates. Using quantum control methods, we consider several optimization problems whose global solutions realize the gate in a chain of three qubits with XY Heisenberg interaction. Applying a minimum number of control pulses assuring a fidelity above 99 % in the ideal case, we design stable gates that are less sensitive to variations in the interqubits couplings. The most stable gate has the fidelity above 91 % with variations about 0.1 %, for up to 10 % variation in the nominal couplings. We perturb the system by introducing a single source of 1 / f noise that affects all the couplings. In order to quantify the performance of the proposed optimized gates, we calculate the fidelity of a large set of optimized gates under prescribed levels of coupling perturbation. Then, we run multifractal analysis on the sequence of attained fidelities. This way, gate performance can be assessed beyond mere average results, since the chosen multifractality measure (the width of the multifractal spectrum) encapsulates into a single performance indicator the spread of fidelity values around the mean and the presence of outliers. The higher the value of the performance indicator the more concentrated around the mean the fidelity values are and rarer is the occurrence of outliers. The results of the multifractal analysis on the fidelity sequences demonstrate the effectiveness of the proposed optimized gate implementations, in the sense they are rendered less sensitive to variations in the interqubits coupling strengths