Achievement of very low disease activity and remission treatment targets is associated with reduced radiographic progression in patients with psoriatic arthritis treated with certolizumab pegol

Background: Several disease activity measures and thresholds have been recommended as psoriatic arthritis (PsA) treatment targets, although consensus on the most appropriate assessment tool is lacking.1 Reports suggest low disease activity (LDA) and remission may be associated with minimal structural progression in PsA.2 Objectives: To report the relationship between PsA disease activity and structural progression over 216 weeks' (wks) treatment with certolizumab pegol (CZP), an Fc-free, PEGylated, tumour necrosis factor inhibitor (TNFi) that has shown long-term efficacy and safety in PsA.3 Methods: Patients (pts) enrolled in RAPID-PsA (NCT01087788) with active PsA (≥3 tender joints; ≥3 swollen joints; ESR ≥28 mm/hour and/or CRP >upper limit of normal) who had failed treatment with ≥1 csDMARD were randomised 1:1:1 to CZP 200 mg every 2 wks (Q2W), CZP 400 mg every 4 wks (Q4W), or placebo (PBO). All CZP pts received CZP 400 mg at Wks 0/2/4. PBO pts were re-randomised to CZP 200 mg Q2W or 400 mg Q4W at Wk 16 or 24.3 Pts were heterogenous for structural damage and disease duration at baseline. Disease activity was assessed using minimal disease activity (MDA) criteria (

MDA:

5-6/7 criteria; very LDA [VLDA]: 7/7 criteria), Psoriatic Arthritis Disease Activity Score (PASDAS) (

LDA:

>1.9-≤3.2; remission: ≤1.9), or Disease Activity Index for Psoriatic Arthritis (DAPSA) (

LDA:

>4-≤14; remission: ≤4). Radiographs were read in four reading campaigns using the van der Heijde modified Total Sharp Score (mTSS) for PsA. A risk of structural progression (RSP) subgroup (baseline mTSS >median for all pts) was also assessed. Mean change from baseline (CFB) in mTSS and associations with disease activity states were estimated using a hierarchical linear mixed effects model (fixed effects: reading campaign/interactions of concurrent disease activity levels with time; random effects: pt/reading campaign nested within pt) which allowed mean mTSS trajectory, and impact of disease activity levels on this, to differ over time. Results: 407/409 randomised pts were assessed for mTSS at least once. At Wk 0, mean (standard deviation) DAPSA=44.5 (22.7), PASDAS=6.0 (1.1). 3/409 (0.7%) pts reported MDA. The proportion of pts achieving remission/VLDA states increased to Wk 216, as did estimated mean mTSS. Estimated mean mTSS CFB remained low overall (0.46 at Wk 216; standard error 0.16; Figure). Across disease activity measures, remission/VLDA states were associated with mTSS estimated mean CFB ≤0 in both the overall group and RSP subgroup (Table). Conclusion: These data indicate that achievement of remission in PsA is important to prevent further structural damage, particularly in pts with pre-existing structural changes. This supports the rationale for strict disease activity targets.