Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study

Abstract

Introduction In the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-naïve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA. Methods In the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher’s exact test. Missing data were imputed using non-responder imputation. Results By week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 ( p = 0.002) endpoint, minimal disease activity ( p = 0.016), and very low disease activity ( p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use. Conclusion In PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance. Electronic supplementary material The online version of this article (10.1007/s40744-020-00250-3) contains supplementary material, which is available to authorized users.

Persistence and effectiveness of the IL-12/23 pathway inhibitor ustekinumab or tumour necrosis factor inhibitor treatment in patients with psoriatic arthritis: 1-year results from the real-world PsABio Study

“…The differential importance of MTX co-therapy on persistence with ustekinumab versus TNFi demonstrated in this real-world study supports results from the long-term SPIRIT-H2H extension randomised controlled trial data 12. While ustekinumab persistence is independent of co-therapy with MTX, TNFi persistence without MTX is shorter than with MTX and shorter than ustekinumab with/without MTX.…”

“…33 The differential importance of MTX co-therapy on persistence with ustekinumab versus TNFi demonstrated in this real-world study supports results from the long-term SPIRIT-H2H extension randomised controlled trial data. 12 While ustekinumab persistence is independent of co-therapy with MTX, TNFi persistence without MTX is shorter than with MTX and shorter than ustekinumab with/without MTX. This may be interpreted as a function of several mechanisms: patients receiving a TNFi may develop neutralising antidrug antibodies when MTX is not given; with ustekinumab, the risk of such antidrug antibodies is described as minimal.…”

“…Owing to the significant disease heterogeneity, number of available drugs and limited head-to-head clinical trials in PsA,12 13 treatment selection is challenging. Treatment persistence is important when managing patients who require long-term treatment, in whom poor adherence (the degree of conformity to treatment recommendations relating to dose and frequency) and poor persistence can lead to suboptimal outcomes 14 15.…”

Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial

“…8 9 Although biological agents are effective in treating PsA, 10 approximately 25%-40% of patients do not achieve at least 20% improvement in American College of Rheumatology score (ACR20), and clinical REM and minimal disease activity (MDA) are often short-lived. [11][12][13][14][15][16][17][18][19] Lack of efficacy frequently leads to treatment switching or discontinuation, which may negatively affect patients' clinical outcomes and increase treatment costs, [20][21][22][23][24] revealing a need for well-tolerated treatments with sustained efficacy.…”

Papel del eje intestino-piel-articulaci�n en enfermedades inmunomediadas. Papel de nuevas terapias con JAKinibs selectivos e inhibidores IL23p19

“…Además de la inhibición de la IL-23, se han evaluado diferentes tratamientos dirigidos a moléculas efectoras de la inmunidad tipo 3 como la IL-17 y la IL-22. La inhibición de la IL-17 ha sido revisada ampliamente y los ensayos clínicos, tanto de secukinumab como de ixekizumab (los dos agentes que bloquean la IL-17) han demostrado efectividad y han resultado muy valiosos en el entendimiento de las enfermedades inmunomediadas relacionadas con PsO [116][117][118][119][120] y SpA 117,[121][122][123][124] . De forma interesante, se ha reportado que la inhibición de IL-17 en pacientes con EII resulta en un agravamiento del daño intestinal, probablemente relacionado con una disminución de la función de barrera 125,126 .…”