Background/Purpose: The efficacy of ixekizumab (IXE) and adalimumab (ADA) in patients with psoriatic arthritis (PsA) has been previously reported using ACR 50 and Psoriasis Area and Severity Index (PASI) 100 responses.^1,2 To minimize confounding effects, in this analysis we assessed the efficacy of either IXE or ADA monotherapy on reduction of pain beyond measurable inflammation in patients with active PsA and with low C-reactive protein (CRP) (< 5mg/L) at baseline.

Methods: SPIRIT-H2H (NCT03151551) was a 52 week (W), multicenter, randomized, open-label, parallel-group, assessor-blinded study evaluating the efficacy and safety of IXE vs ADA.¹ Participants were randomized (1:1) to approved-label dosing of IXE or ADA. This post-hoc analysis included only patients treated with IXE or ADA as monotherapy and with low CRP (< 5mg/L) at baseline. Changes in joint pain were measured using PsA Patient’s Assessment of Pain Visual Analog Scale (VAS). We stratified patients into four categories by two measures of inflammation:

1. Sustained low inflammation either by
1. CRP < 5 mg/L during W4-24 or
2. ≥ 50% improvement in swollen joint count (SJC) during W8-24.
2. Fluctuating inflammation either by
1. CRP ≥ 5 mg/L at least once between W4-24 or
2. < 50% improvement in SJC at least once between W8-24.

Results: Ninety-five monotherapy patients with a CRP < 5mg/L at baseline were included in this analysis. Baseline characteristics were similar between both treatment arms. In patients with fluctuating inflammation as measured by CRP, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients at W16 (IXE: -31.64, ADA: -25.33, Fig. 1b) that was sustained up to W52 (IXE: -47.69, ADA: -20.67, Fig. 1b). There was significance in favor of IXE at W32 (p = 0.0045) and W52 (p = 0.0288, Fig. 1b). In patients with sustained low inflammation as measured by CRP, there was no difference in improvement in joint pain between IXE and ADA-treated patients (Fig.1a). In patients with sustained improvement in joint swelling as assessed by SJC, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients from W4 (IXE: -17.47, ADA: -10.42, Fig. 1c) that was sustained through W52 (IXE: -43.16, ADA: -32.62, Fig. 1c). In patients with fluctuating improvement in joint swelling as assessed by SJC, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients from W16 (IXE: -22.00, ADA: -19.31, Fig. 1d) that was sustained through W52 (IXE: -28.57, ADA: -13.27, Fig. 1d).

Conclusion: This analysis suggests a different pattern of pain improvement in patients with low baseline CRP treated with IXE or ADA monotherapy, with a favorable pain reduction outcome for IXE-treated patients, even when inflammation is fluctuating as measured by CRP or SJC improvement. This analysis supports the hypothesis that IXE improves joint pain in PsA patients with and without measurable inflammation.

References:

1. Mease et al. Ann Rheum Dis. 2020;79(1):123-31.
2. Smolen et al. Rheumatol Ther. 2020;7(4):1021-35.

Figure 1. All patients had low baseline CRP (CRP < 5mg/L) and were treated with IXE or ADA as monotherapy. (a) Change in joint pain from baseline of patients with sustained low inflammation measured by CRP in IXE and ADA treatment groups. (b) Change in joint pain from baseline of patients with fluctuating inflammation measured by CRP in IXE and ADA treatment groups. (c) Change in joint pain from baseline of patients with sustained improvement in SJC in IXE and ADA treatment groups. (d) Change in joint pain from baseline of patients with fluctuating improvement in SJC in IXE and ADA treatment groups. *p value ≤ 0.05, **p value ≤ 0.01. Some patients were excluded from analysis due to missingness at visits.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/ixekizumab-shows-a-pattern-of-pain-improvement-in-patients-with-and-without-measurable-inflammation-in-psoriatic-arthritis/