Background/Purpose:

To compare 1) extra-articular manifestations, 2) baseline comorbidities, and 3) adverse event (AE) rates with long-term adalimumab (ADA) therapy in patients (pts) treated in clinical trials for established ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA).

Methods:

This post hoc analysis was performed in 3 studies: 1) ATLAS, a phase 3, randomized, double-blind (DB), multicenter study in US and Europe in pts with active AS who had inadequate response, or were intolerant to ≥1 nonsteroidal anti-inflammatory drug (NSAID); 2) M03-606, conducted in Canada with the same study design as ATLAS, and 3) ABILITY-1, a phase 3, multinational, randomized, DB, multicenter study in pts with active nr-axSpA (pts with past/present diagnosis of psoriasis were excluded). Pts were randomized to receive ADA 40 mg every other week (wk) or placebo for 24 wks followed by open-label ADA for up to 260 wks in ATLAS and M03-606, and up to 156 wks in ABILITY-1. Pts who received ≥1 dose of ADA at any time during the study were analyzed (Any ADA set). AE frequency and events/100 patient-years (E/100 PY) of ADA exposure were summarized by study indication with the AS studies combined.

Results:

The Any ADA population in the ATLAS/M03-606/ABILITY-1 studies was n=311/82/183, respectively. The Any ADA safety population was n=393 for AS and n=190 for nr-axSpA. Mean age was similar in AS and nr-axSpA pts, ranging from 37-42 yrs and about 80% of both AS and nr-axSpA pts were HLA-B27 positive. AS pts were predominantly male and had longer duration of disease diagnosis compared to nr-axSpA pts. Mean duration of SpA symptoms was >10 yrs in the nr-axSpA study; however, it was not collected in the AS studies (Table 1). At BL uveitis and IBD were less frequent in nr-axSpA pts compared to AS pts. Among pts exposed to ADA (1543.9 PY of exposure in AS, 412.2 PY in nr-axSpA), the incidence of serious AEs was similar in both populations (10.8 vs. 10.9 E/100 PY, AS vs. nr-axSpA). The malignancy rate in AS studies was 0.8 E/100 PY and 0 in nr-axSpA. There was 1 death in the AS studies (<0.1 E/100 PY) and 2 in nr-axSpA pts (0.5 E/100 PY); none were considered related to ADA. (Table 2)                    

Table 1. Baseline Demographic and Disease Characteristics
	AS		nr-axSpA
	ATLAS N = 311	M03-606 N = 82	ABILITY-1 N = 183
Demographics
Age, mean (years)	42.3	40.9	37.9
Male, n (%)	233 (74.9)	65 (79.3)	83 (45.4)
HLA-B27 +, n (%)	245 (78.8)	69 (84.1)	144 (78.7)
Duration of disease diagnosis, mean (years)	10.9	13.3	2.8
Symptom duration, mean (years)	–	–	10.1
SpA Disease   Characteristics
CRP elevated, n (%)	211 (67.8)	60 (73.2)	65 (35.5)
BASDAI, mean (0–10)	6.3	6.3	6.5
PtGA, mean (VAS 0–10)	6.4	6.7	6.8
PGA, mean (VAS 0–10)	5.7	6.5	5.7
Total back pain, mean (VAS 0–10)	6.5	7.0	7.0
Uveitis, n (%)	95 (30.2)	32 (39.0)	22 (12.0)
Inflammatory bowel disease, n (%)	27 (8.6)	9 (11.0)	8 (4.3)
Psoriasis*, n (%)	34 (10.9)	11 (13.4)	0
*A past or present diagnosis of psoriasis was an exclusion criterion for ABILITY-1. AS, ankylosing spondylitis; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; CRP, C-reactive protein; nr-axSpA, non-radiographic axial spondyloarthritis; PGA; physician global assessment of disease activity; PtGA, patient global assessment of disease activity; SpA, spondyloarthritis.

                  

Table 2. Adverse Events
	ASa Any ADA Safety Population (N = 393; 1543.9 PY)	nr-axSpAb Any ADA Safety Population (N = 190; 412.2 PY)
	E/100 PY	E/100 PY
Any AE	343.5	320.7
Any Serious AE	10.8	10.9
Any Infection	92.4	102.6
Serious Infections	1.4	2.4
Cardiac Disorder	1.0	0.2
Any Malignancy	0.8	0
Lymphoma	<0.1	0
Hematologic Disorders	1.0	1.5
Psychiatric Disorders	7.8	9.9
Gastrointestinal Disorders	27.0	33.7
Liver Events	0.8	0.5
Inflammatory bowel disease (new onset or worsening)c	0.6	0.5
Psoriasis (new onset or worsening)	2.7	0.5
Uveitis (new onset or worsening)d	3.0	1.5
Deaths	<0.1	0.5
aATLAS + M03-606 studies. bABILITY-1 study. cIncludes inflammatory bowel disease, Crohn’s disease and colitis ulcerative. dIncludes uveitis, iritis and iridocyclitis. Any ADA = patients who received ≥1 dose of ADA at any time during the study. Not all events within larger system organ categories are reported in this table. MedDRA version 15.1. ADA, adalimumab; AE, adverse event; AS, ankylosing spondylitis; E, event; nr-axSpA, non-radiographic axial spondyloarthritis; PY, patient-year.

Conclusion:

Enrolled pts with AS and nr-axSpA were generally similar in terms of demographics and BL disease activity. Although the SpA-related comorbidities of IBD and uveitis were more commonly reported in AS pts as compared to nr-axSpA pts at BL, reported AE rates were generally similar between pts with AS and nr-axSpA. This indicates a similar safety profile for ADA treatment in all pts with axial SpA.

---

« Back to ACR/ARHP Annual Meeting 2014

ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-baseline-extra-articular-manifestations-comorbidities-and-long-term-safety-in-patients-treated-with-adalimumab-for-ankylosing-spondylitis-and-non-radiographic-axial-spondyloarthritis/