Impact of HLA-B27 on Patient Profile and Treatment Response in As Patients Treated with Anti-TNF in Canadian Real-World

Isabelle Fortin¹, Maqbool Sheriff², Proton Rahman³, Michael Starr⁴, Wojciech Olszynski⁵, Sanjay Dixit⁶, Viktoria Pavlova⁷, Derek Haaland⁸, Emmanouil Rampakakis⁹, Eliofotisti Psaradellis¹⁰, Brendan Osborne¹¹, Karina Maslova¹², Allen J Lehman¹², Francois Nantel¹³ and Cathy Tkaczyk¹¹, ¹Centre de Rhumatologie De l’Est du Quebec, Rimouski, QC, Canada, ²Nanaimo Regional General Hospital, Nanaimo, BC, Canada, ³Rheumatology, St Claires Mercy Hospital, St Johns, NF, Canada, ⁴Rheumatology, Mcgill University, Pointe-Claire,, QC, Canada, ⁵103 Midtown Professional Center, Rheumatology Associates of Saskatoon, Saskatoon, SK, Canada, ⁶Rheumatology, McMaster University Hamilton, Burlington, ON, Canada, ⁷Ancaster Medical Centre, Ancaster, ON, Canada, ⁸Rheumatology, Clinical Immunology & Allergy, McMaster University, Barrie, ON, Canada, ⁹JSS Medical Research, St-Laurent, QC, Canada, ¹⁰JSS Medical Research, Montreal, QC, Canada, ¹¹Medical Affairs, Janssen Inc., Toronto, ON, Canada, ¹²Janssen Inc., Toronto, ON, Canada, ¹³19 Green belt Dr, Janssen Inc., Toronto, ON, Canada

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Ankylosing spondylitis (AS) and anti-TNF therapy

Session Information

Date: Sunday, November 13, 2016

Session Title: Spondylarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment - Poster I: Axial and Peripheral Spondyloarthritis – Clinical Aspects, Imaging and Treatment

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: The human leukocyte antigen (HLA)-B27 allele is one of the strongest known genetic factors associated with the development of ankylosing spondylitis, however, previous studies have shown that approximately 10-25% of AS patients are HLA-B27 negative (HLA-). The aim of this analysis was to compare the profile of HLA – and HLA+ AS patients initiating anti-TNF treatment in Canadian routine clinical care.

Methods:

BioTRAC is an ongoing, prospective registry of patients initiating treatment with infliximab (IFX) or golimumab (GLM) for RA, AS, or PsA, or with ustekinumab for psoriasis. Patients eligible for this analysis included AS patients treated with IFX or GLM, enrolled since 2005 and 2010, respectively with available information on HLA B27 status. Descriptive statistics were used to assess patient and disease characteristics at Baseline and Month 12. Multivariate general linear models were used to assess the impact of HLA status on BASFI, BASDAI and ASDAS at Month 12 while adjusting for age, gender, disease duration, anti-TNF type, and baseline scores.

Results:

A total of 147 HLA+ and 78 HLA- AS patients were included, of which 93 had available data at Month 12 (62 HLA+, 31 HLA-). Table 1 summarizes the baseline patient characteristics and disease parameters by HLA status. HLA+ patients were significantly younger compared to HLA- patients both at diagnosis (32.2 vs. 46.8 years; P=0.001) and at anti-TNF initiation (42.1 vs. 48.2 years; P=0.002). Furthermore, HLA+ patients had significantly higher disease duration (7.7 vs. 3.9 years; P=0.002) and were more likely to be male (69.0% vs. 42.1%; P<0.001). Geographic distribution was comparable between HLA+ and HLA- groups (P=0.886). With respect to disease parameters, baseline BASDAI, BASFI and ASDAS were significantly higher in the HLA- group (P < 0.05), as was the proportion of HLA- patients reporting very high ASDAS disease activity (62.5% vs. 38.2%). Mean baseline CRP levels, although higher in HLA- patients compared to HLA+ patients (16.7 vs. 10.5 mg/L), were not found to be significantly different between groups (P=0.085).

Upon adjusting for potential confounders, HLA+ patients experienced greater improvements from baseline to Month 12 in BASDAI (-2.13 vs. -0.24; P=0.008), BASFI (-1.64 vs. 0.11; P=0.030), and ASDAS (-0.95 vs. -0.26; P=0.067). At Month 12, ASDAS DA categories were found to be statistically comparable across both groups (P=0.396), although a lower proportion of HLA – patients reported inactive-moderate disease (30.0% vs. 51.2%).

Table 1. Patient and Disease Characteristics at anti-TNF Initiation by HLA Status

Parameter	HLA+ (N=147)	HLA- (N=78)	P-value
Age, years, mean (SD)	42.1 (13.2)	48.2 (13.4)	0.002
Age at diagnosis, mean (SD)	32.2 (9.0)	46.8 (14.0)	0.001
Disease duration, years, mean (SD)	7.7 (10.3)	3.9 (4.4)	0.002
Gender, male, n (%)	98 (69.0)	44 (31.0)	< 0.001
Anti-TNF at baseline
Infliximab, n (%)	27 (18.4)	15 (19.2)	0.504
Golimumab, n (%)	120 (81.6)	63 (80.2)
CRP levels, mg/L, mean (SD)	10.5 (20.2)	16.7 (29.2)	0.084
BASDAI, mean (SD)	5.9 (2.2)	6.6 (1.7)	0.022
BASFI, mean (SD)	5.0 (2.6)	5.9 (2.2)	0.026
ASDAS, mean (SD)	3.2 (0.96)	3.7 (0.90)	0.002
ASDAS Disease Activity (DA), %
Inactive DA	2.7	0.0
Moderate DA	5.5	3.6	0.022
High DA	53.6	33.9
Very high DA	38.2	62.5

Conclusion: In this Canadian real-world cohort, HLA- AS patients were found to be demographically distinct from HLA+ patients and present with more advanced disease at baseline. Furthermore, HLA- was identified as an independent predictor of worse treatment outcomes, highlighting the importance of early diagnosis and management of HLA- AS patients.

Disclosure: I. Fortin, None; M. Sheriff, Janssen Inc., 5; P. Rahman, Janssen Inc., 5; M. Starr, Janssen Inc., 5; W. Olszynski, Janssen Inc., 5; S. Dixit, Janssen Inc., 5; V. Pavlova, Janssen Inc., 5; D. Haaland, None; E. Rampakakis, employee of JSS Medical Research, 3; E. Psaradellis, employee of JSS Medical Research, 3; B. Osborne, Employee of Janssen Inc., 3; K. Maslova, Employee of Janssen Inc., 3; A. J. Lehman, Employee of Janssen Inc., 3; F. Nantel, Employee of Janssen Inc., 3; C. Tkaczyk, Employee of Janssen Inc., 3.

To cite this abstract in AMA style:

Fortin I, Sheriff M, Rahman P, Starr M, Olszynski W, Dixit S, Pavlova V, Haaland D, Rampakakis E, Psaradellis E, Osborne B, Maslova K, Lehman AJ, Nantel F, Tkaczyk C. Impact of HLA-B27 on Patient Profile and Treatment Response in As Patients Treated with Anti-TNF in Canadian Real-World [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/impact-of-hla-b27-on-patient-profile-and-treatment-response-in-as-patients-treated-with-anti-tnf-in-canadian-real-world/. Accessed October 19, 2021.

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