Background/Purpose

Approximately two-thirds of patients (pts) with psoriatic arthritis (PsA) experience progressive joint damage associated with varying degrees of disability. Here we present the 1-year effect of IL-17A inhibition with secukinumab on radiographic progression in pts with active PsA enrolled in a 2-year, multicenter, randomized, double-blind, placebo (PBO)-controlled, phase 3 trial (FUTURE 1; NCT01392326).

Methods

606 adults with moderate to severe PsA were randomized to PBO or one of two secukinumab treatment arms: secukinumab 10 mg/kg i.v. followed by 75 mg s.c. (10 IV→75 SC) or 150 mg s.c. (10 IV→150 SC). All pts were assessed for joint response at Week (Wk) 16 (based on ≥ 20% improvement in tender and swollen joint counts). PBO-treated pts were re-randomized to secukinumab 75 or 150 mg s.c. at Wk 16 (non-responders) or Wk 24 (responders). The van der Heijde total modified Sharp scores (mTSS), and erosion and joint space narrowing (JSN) scores were determined at baseline, Wks 16/24 (depending on response) and Wk 52. The effect of secukinumab on radiographic progression from baseline to Wk 24 was evaluated using a non-parametric ANCOVA model, with linear extrapolation for pts who had x-ray assessments at Wk 16. Exploratory analyses assessed the proportion of pts with no structural progression (defined as change from baseline in mTSS ≤ 0.5) and maintenance of this effect over time.

Results

The changes from baseline in mTSS, erosion and JSN scores demonstrated that secukinumab-treated pts had significantly less progression from baseline to Wk 24 compared with PBO-treated pts, regardless of whether pts had received prior therapy with a TNF inhibitor, were on secukinumab monotherapy, or were receiving concomitant methotrexate (MTX; Table). Inhibition of joint structural damage was sustained with secukinumab through Wk 52. Analysis of PBO pts who switched to secukinumab showed a greater mean change from baseline in mTSS for the PBO group from baseline to Wk 24 (mean increase of 0.48) vs. the period from Wk 24 to Wk 52 when pts had been switched to secukinumab (mean decrease of –0.03), providing additional support for efficacy. Analyses of pts who had x-rays at both Wk 16/24 and 52 showed that the proportion of pts who experienced no progression from randomization to Wk 24 vs. the period from Wk 24 to Wk 52 was consistently high in the secukinumab groups: 92.3% vs. 85.8%, respectively, for 10 IV→75 SC and 82.3% vs. 85.7% for 10 IV→150 SC. In pts initially randomized to PBO, 75.7% had no progression from randomization to Wk 24 and this increased to 86.8% for the period from Wk 24 to Wk 52 following active treatment with secukinumab (P< 0.05).

Table.  Radiographic progression at Week 24 by treatment group
Week 24 (Mean change from baseline)	Secukinumab 10 mg/kg IV → 75 mg SC n = 202	Secukinumab 10 mg/kg IV → 150 mg SC n = 202	PBO n = 202
mTSS	0.02†	0.13†	0.57
Erosion score	0.08†	0.04ǂ	0.35
JSN score	–0.06†	0.10	0.23
TNF-naïve/IR	n = 142/n = 60	n = 143/n = 59	n = 143/n = 59
mTSS	–0.06†/0.21	0.15/0.10†	0.57/0.58
Erosion score	0/0.25	0.02/0.08ǂ	0.29/0.50
JSN score	–0.06†/–0.05	0.13/0.02	0.28/0.09
Concomitant MTX use, yes/no	n = 122/n = 80	n = 121/n = 81	n = 125/n = 77
mTSS	–0.07†/0.14	0.14/0.12	0.57/0.58
Erosion score	0.01†/0.17	0.04†/0.02	0.34/0.37
JSN score	–0.08/–0.03	0.10/0.10	0.24/0.21
†P < 0.05 vs. placebo; ǂP < 0.01 vs. placebo JSN, joint space narrowing; mTSS, modified total Sharp score; MTX, methotrexate; TNF-naïve/IR, tumor necrosis factor inhibitor naïve/inadequate responder P-values based on a non-parametric ANCOVA model.

 Conclusion

In patients with active PsA, secukinumab significantly inhibited radiographic progression at 24 wks regardless of prior TNF inhibitor therapy status or concomitant MTX administration; inhibition was sustained through Wk 52.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/secukinumab-a-monoclonal-antibody-to-interleukin-17a-provides-significant-and-sustained-inhibition-of-joint-structural-damage-in-active-psoriatic-arthritis-regardless-of-prior-tnf-inhibitors-or-conc/