Ixekizumab as Effective, if not More Effective as TNFi, JAKi, IL-12/23i for PsA Treatment

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Ixekizumab was rapidly effective in treating psoriatic arthritis (PsA) in a recent study, was as fast as TNF and JAK inhibitors, and exceeded the speed of IL-12/23 and IL-23 inhibitors.¹

“The Psoriatic Arthritis Observational Study of Persistence of Treatment (PRO-SPIRIT) is a multinational, prospective study investigating the real-world use of biological/ targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) in PsA treatment, with a primary objective of describing persistence at 24 months among patients initiating a new b/tsDMARD,” lead investigator Lars Erik Kristensen, MD, PhD, chief scientific officer, Parker Institute, Demark, and colleagues wrote.1 “While randomized controlled trials are the gold standard for exploring treatment efficacy in the target population, real-world evidence (RWE) is vital for fully capturing the effectiveness of PsA therapies in the heterogeneous PsA population, and facilitates the comparison of a greater number of drugs with different mechanisms of action (MoAs).”²

Kristensen and colleagues reported data from an interim analysis of the PRO-SPIRIT study, from 3 months of evaluation of RWE in patients with PsA prescribed with advanced treatment including IL-17A inhibitors;ixekizumab or secukinumab, IL-12/23 inhibitors, IL-23 inhibitors, tumor necrosis factor (TNF) inhibitors (TNFi), or Janus kinase (JAK) inhibitors (JAKi).

The investigators analyzed data from 1192 patients from across 6 countries. They found that patients receiving ixekizumab had longer disease duration at baseline and higher previous b/tsDMARDs experience than patients starting TNFi and secukinumab. These patients also had less concomitant csDMARD use than TNFi and JAKi use.

Comparing treatment regimens, Kristensen and colleagues found that compared with patients that used TNFi, patients using ixekizumab had similar improvements in clinical Disease Activity in PsA (cDAPSA) but significantly greater improvements in body surface area affected by psoriasis (BSA; P <.05) and global assessments (GA), including physician GA and patient GA. Compared to patients receiving versus IL-12/23i and IL-23i (pooled), patients receiving ixekinumab had significantly greater improvements in cDAPSA and patient GA.¹

Patients receiving ixekinumab had improvements in JDA as fast as patients receiving JAKi. The investigators also found that, according to ad hoc analysis, more patients with active PsA, defined as a BSA score of at least 3, achieved minimal disease activity with ixekizumab than with JAKi or IL-12/23i. Improvements in tender (TJC) and swollen joint counts (SJC) and cDAPSA were significantly greater with ixekinumab (LSM difference, −3.6; P <.01; LSM difference, −2.4; P <.05 and LSM difference, −8.4; P <.001) than with IL-12/23i and IL-23i (pooled). Similarly, those who had initiated IXE (p<0.01) exhibited significantly greater improvements in BSA than those who had initiated either an IL-12/23i or IL-23i.¹

Notably, patient responses to secukinumab varied by dosage, and was found to be less effective to similarly effective as ixekimumab.

“This RWE study confirms the efficacy of ixekinumabas reported in RCTs, which is consistent regardless of patient baseline characteristics or clinical domain involvement, and additionally provides valuable comparative analyses among different treatment groups and treatment populations in a real-world setting. This RWE brings rheumatologists one step closer to holistic care of the patient and individualizing treatment options for patients with PsA that focus on both early responses in the joints and skin as well as baseline disease severity,” Kristensen and colleagues concluded.¹

REFERENCES
1. Kristensen LE, Ng KJ, Ngantcha M, et alComparative early effectiveness across 14 PsA drugs and 5 classes of PsA treatment: 3-month results from the PRO-SPIRIT study. RMD Open 2024;10:e004318. doi: 10.1136/rmdopen-2024-004318

2. Cinelli E, Fabbrocini G, Megna M. Real-world experience versus clinical trials: pros and cons in psoriasis therapy evaluation. Int J Dermatol 2022;61:e107–8. doi:10.1111/ijd.15644