Background/Purpose: Adalimumab (ADA) is indicated for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Patients (pts) with peripheral spondyloarthritis (SpA) not previously diagnosed with psoriasis or PsA (non-PsA), presenting primarily with arthritis, enthesitis and/or dactylitis, may also benefit from anti-TNF therapy. ABILITY-2, the first randomized controlled trial to use the ASAS peripheral SpA criteria¹ to classify pts for study entry, evaluated the efficacy and safety of ADA in pts with active non-PsA peripheral SpA. 

Methods: ABILITY-2 is an ongoing, multicenter phase 3 study. Eligible pts were age ≥18 yrs, fulfilled ASAS peripheral SpA criteria, did not have a diagnosis of psoriasis, PsA, or AS, and had inadequate response or intolerance to NSAIDs. Pts were randomized 1:1 to ADA 40 mg every other wk or placebo (PBO) for 12 wks followed by a 144-wk open-label extension. Primary endpoint was the proportion of pts achieving peripheral SpA response criteria (PSpARC 40) at wk 12: ≥40% improvement (≥20 mm absolute improvement in VAS) from baseline (BL) in Pt’s Global Assessment of Disease Activity (PGA) and of pain (PGA-pain) and ≥40% improvement in ≥1 of the following: swollen joint count (SJC) and tender joint count (TJC); Enthesitis Count, or Dactylitis Count. Other outcomes analyzed included Physician’s Global Assessment (PhGA), BASDAI, enthesitis indices, PSpARC 20/50/70 responses, HAQ-S, and SF-36v2. Adverse events (AE) were collected throughout the study.

Results: 165 pts (ADA 84/PBO 81) were randomized. BL demographics/disease characteristics were similar between groups, except for mean age and % pts with dactylitis count>0. BL characteristics include (ADA/PBO): 57/52% female, 67/56% HLA-B27+, mean TJC 13.0/13.6, mean SJC 6.1/7.3, mean enthesitis count 6.7/7.3, and dactylitis count 0.4/0.7. At Wk 12, the % of ADA pts achieving PSpARC 40 was higher vs. PBO (P=0.006) (table), primarily due to the proportion of patients meeting the PGA, PGA-pain, and TJC/SJC components. Overall, improvement based on other outcomes was greater with ADA vs. PBO. AE incidence rates were similar [ADA/PBO (%)]: any AEs (54.8/54.3), serious AEs (1.2/1.2), and infectious AEs (21.4/28.4); there were no serious infections, TB, or malignancies during the double-blind period.

Conclusion: Adalimumab significantly improved signs, symptoms, and physical function of pts with active non-PsA peripheral SpA and was well-tolerated. ABILITY-2 results suggest that ADA may be an effective treatment option for non-PsA peripheral SpA pts with inadequate response or intolerance to NSAIDs. Further, these results suggest that the PSpARC assessment instrument, pioneered in this study to evaluate this patient population, is a responsive and discriminative outcome measure.  

 

Table. Week 12 Efficacy Outcomes
		ADA N=84	PBO N=81	P valuea
Primary endpointb PSpARC 40, %		39.3	19.8	0.006
Proportion of patients achieving improvement in each PSpARC 40 componentc (≥40% improvement, plus ≥20 mm improvement in PGA and PGA-pain VAS)
PGA, %		54.3	28.8	<0.001
PGA pain, %		53.7	31.3	0.004
TJC/SJC, %		57.3	29.6	<0.001
Enthesitis, %		51.2	42.0	0.237
Dactylitis, %		13.6	18.5	0.392
Other efficacy endpoints
PSpARC 20b, %	56.0		37.0	0.015
PSpARC 50b, %	34.5		11.1	<0.001
PSpARC 70b, %	22.6		3.7	<0.001
PGAd (VAS 0–100), mm	-27.5		-16.4	0.003
PGA-paind (VAS 0–100), mm	-28.9		-17.1	0.001
PhGAd (VAS 0–100), mm	-32.2		-18.2	<0.001
BASDAId	-2.1		-1.0	0.003
TJCd (0–78)	-5.9		-1.8	<0.001
SJCd (0–76)	-3.6		-3.1	0.045
Leeds enthesitis indexd (0–6)	-0.8		-0.1	<0.001
SPARCC enthesitis indexd (0–16)	-1.7		-0.7	<0.001
Dactylitis countd (0–20)	-0.2		-0.3	0.808
SF-36v2 PCSe	6.7		2.4	<0.001
HAQ-S scored	-0.3		-0.2	0.051
Values are mean change unless otherwise indicated; Ns may vary by outcome. aADA vs. PBO; bNRI; cObserved analysis; dLOCF; eObserved data (N=83/79, ADA/PBO). ADA, adalimumab; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; HAQ-S, Health Assessment Questionnaire modified for spondyloarthropathies; PBO, placebo; PGA, patient’s global assessment of disease activity; PGA-pain, patient’s global assessment of pain; PhGA, physician’s global assessment; PSpARC, peripheral spondyloarthritis response criteria; PSpARC 20, ≥20% (≥10 mm in VAS) improvement; PSpARC 50, ≥ 50% (≥20 mm in VAS) improvement; PSpARC 70, ≥70% (≥30 mm in VAS) improvement; SF-36v2 PCS, short form-36 health status survey version 2 physical component summary; SJC, swollen joint count; SPARCC, Spondyloarthritis Research Consortium of Canada; TJC, tender joint count.

Reference

1. Rudwaleit M et al. Ann Rheum Dis 2011;70:25–31.

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