Impact of HLA- B27 on Pa3ent Profile and Treatment Response in AS Pa3ents Treated with An3- TNF in Canadian Real- World

Transcription

1 Impact of HLA- B27 on Pa3ent Profile and Treatment Response in AS Pa3ents Treated with An3- TNF in Canadian Real- World For%n I, Sheriff M, Rahman P, Starr M, Olszynski W, Dixit S, Pavlova V, Haaland D, Rampakakis E, Psaradellis E, Osborne B, Lehman AJ, Nantel F, Tkaczyk C

2 Disclosures CME, Research, Honoraria: Abbvie Amgen BMS Eli Lilly Janssen Pfizer UCB

3 Introduc3on The human leukocyte an3gen (HLA)- B27 allele is one of the strongest known gene3c factors associated with the development of ankylosing spondyli3s (AS) Previous studies have shown that approximately 10-25% of AS pa3ents are HLA- B27 nega3ve (HLA- ) In the French cohort DESIR, 57,9% are HLA- B27 +, and the propor3on varies depending of the set of diagnos3c criteria

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6 Van Tubergen, A. Nat. Rev. Rheumatol. 11, (2015)

7 Baseline Characteris%cs of The DESIR Cohort Pa3ents were enrolled (inclusion period 2007 to April 2010) if they were aged > 18 years and <50 years and suffering from back pain involving the thoracic, lumbar spine or bubock area from more than 3 months less than 3 years. Such back pain had to fulfil the characteris3cs of inflammatory in accordance to either the Berlin or the Calin criteria. Dougados M, Joint Bone Spine 82, , 2015

8 Introduc3on Real life observa3ons are different from these expected: More HLA- B27 More women Variable response to biologic therapies Observed discrepancies in natural evolu3on and treatment response depending of HLA- B27 +/-

9 Objec3ve To compare the profile of HLA- and HLA+ AS pa3ents ini3a3ng an3- TNF treatment in Canadian rou3ne clinical care

10 Methods - Study Design and Popula3on BioTRAC: Biological Treatment Registry Across Canada Mul3- centre, prospec3ve, observa3onal study Pa3ents treated with infliximab 116 rheumatology prac3ces across Canada Ini3ated in February 2002 and is ongoing Analysis Popula%on 147 HLA+ and 78 HLA- AS pa%ents treated with golimumab or infliximab between Pa3ents were an3- TNFα naïve or treated with one biologic before enrolment Pa3ents were assessed in a standardized fashion every 6 months provided this was as per rou3ne clinical care

11 Methods - Sta3s3cal Methods Descrip3ve sta3s3cs were used to assess pa3ent and disease characteris3cs at Baseline and Month 12 Mul3variate general linear models were used to assess the impact of HLA status on BASFI, BASDAI and ASDAS at Month 12 while adjus3ng for poten3al cofounders age, gender, disease dura3on, an3- TNF type, and baseline scores Poten3al cofounders used were age, gender, disease dura3on, an3- TNF type, and baseline scores

12 Baseline Characteris3cs Parameter Age at diagnosis, years, mean (SD) Age at an3- TNF ini3a3on, years, mean (SD) Disease dura3on, years, mean (SD) HLA+ n = 147 HLA- n = 78 p- value (9.0) 46.8 (14.0) (13.3) 48.2 (13.4) (10.3) 3.9 (4.4) Male gender, % < Canadian region of residence 2, % Mari3me Quebec Ontario Western Sta?s?cal significance denoted by bold and italic font 1 Con3nuous variables compared between groups with Student s t- test. Categorical variables compared between groups with Chi- Square test. 2 Mari3me provinces include Nova Sco3a, New Brunswick, Prince Edward Island and Newfoundland. Western provinces include Bri3sh Columbia, Alberta, Saskatchewan and Manitoba.

13 Baseline BASDAI, BASFI and ASDAS were significantly higher in the HLA- group Mean BASDAI BASDAI 5.9 p= Mean BASFI BASFI p= HLA+ HLA- 0 HLA+ HLA- Mean ASDAS P- value was assessed with Student s t- test. Sta?s?cal significance denoted by bold and italic font HLA+ ASDAS p= HLA-

14 Greater improvements in HLA+ pa3ents arer 12 months in BASDAI, BASFI, and ASDAS Change in BASDAI Change in BASDAI p= HLA+ HLA- Change in BASFI Change in BASFI p= HLA+ HLA- Change in ASDAS Change in ASDAS p= HLA+ HLA- Assessed with mul3variate general linear models upon adjus3ng for age, gender, disease dura3on, an3- TNF type, and baseline scores. Sta?s?cal significance denoted by bold and italic font.

15 Baseline Characteris3cs GO- AHEAD Characteris%cs GLM 50 mg (N=98) PBO (N=100) Gender, male, n (%) 61 (62.2) 52 (52.0) Age (years), mean (SD) 30.7 (7.1) 31.7 (7.2) BMI (kg/m2), mean (SD) 25.6 (4.7) 25.1 (4.9) Disease dura%on since symptom onset, n (%) <1 year 67 (68.4) 65 (65.0) 1 to 2 years 20 (20.4) 19 (19.0) 3 to 5 years 11 (11.2) 16 (16.0) BASDAI (1-10 cm VAS), mean (SD) 6.6 (1.6) 6.4 (1.5) BASFI (1-10- cm VAS), mean (SD) 5.3 (2.4) 4.8 (2.5) SPARCC SI MRI score (0-72), mean (SD) 9.9 (12.3) a 12.7 (15.4) b MRI posi%ve for sacroilii%s 1, n (%) 66 (67.3) 66 (66.0) ASDAS, mean (SD) 3.6 (0.9) 3.5 (0.8) CRP concentra%on (mg/dl), mean (SD) 1.5 (2.9) 1.3 (2.0) CRP > ULN, n (%) 40 (40.8) 41 (41.0) HLA- B27 Posi%ve Status, n (%) 81 (82.7) 82 (82.0) a, n=91; b, n=96 1 Central reader reported the presence or absence of ac3ve inflamma3on of SI joints. Sieper et al. Arthritis Rheum 2015; Epub 07JUL doi: /art

16 GO- AHEAD Efficacité clinique et ac%vité de la maladie jusqu à la semaine 52 Score moyen Score DAS-SA 4,5 Étude à double insu 3,6 2,7 1,8 0,9 Étude de prolonga3on ouverte GLM GLM/GLM PBO PBO/GLM Score moyen (cm) 8,0 6,0 4,0 2,0 Indice d inflammation BASDAI Étude à double insu Étude de prolonga3on ouverte GLM GLM/GLM PBO PBO/GLM Score moyen (cm) 0,0 6,5 5,2 3,9 2,6 1,3 0,0 Indice BAFMI Semaine de l étude Étude à double insu Étude de prolonga3on ouverte GLM GLM/GLM PBO PBO/GLM Semaine de l étude Score moyen (cm) 0,0 Indice BASMI 3,0 Étude à double insu 2,4 1,8 1,2 0,6 0,0 Semaine de l étude Étude de prolonga3on ouverte GLM GLM/GLM PBO PBO/GLM Semaine de l étude van der Heijde et al. EULAR 2016, #SAT0388

17 At baseline, a higher propor3on of HLA- pts reported very high ASDAS disease ac3vity ASDAS Disease Ac%vity at Baseline by HLA Status 100% p=0.022 ASDAS Disease Activity (%) 80% 38.2% 62.5% 60% 40% 53.6% 20% 33.9% 2.7% 5.5% 3.6% 0% HLA+ HLA- Very High High Moderate Inactive P- value was assessed with Chi- Square test. Sta?s?cal significance denoted by bold and italic font.

18 At 12 months, a lower propor3on of HLA- pa3ents reported inac3ve- moderate disease ASDAS Disease Ac%vity at 12 months by HLA Status ASDAS Disease Activity (%) 100% 80% 60% 40% 20% 0% 17.9% 30.8% 25.6% 25.6% HLA+ 30.0% 40.0% 20.0% 10.0% HLA- p=0.396 Very High High Moderate Inactive Arer 12 Months, ASDAS disease ac3vity categories were found to be sta3s3cally comparable across both groups (P=0.396) P- value was assessed with Chi- Square test. Sta?s?cal significance denoted by bold and italic font.

19 Mean baseline CRP levels were not found to be significantly different between groups CRP Levels by HLA Status Mean CRP (mg/l) p= HLA+ HLA- Main predictor of ankylosis: CRP P- value was assessed with Student s t- test.

20 Conclusion In this Canadian real- world cohort, HLA- AS pa3ents were found to be demographically dis3nct from HLA + pa3ents and present with more clinically advanced disease at baseline. Furthermore, HLA- was iden3fied as an independent predictor of worse treatment outcomes, highligh3ng the importance of early diagnosis and management of HLA- AS pa3ents The presence of a sub- group of pa3ent not included in the studies that respond differently to an3- TNF

21 Le traitement par anti-tnfs pourrait ralentir la progression radiographique de la SA : données provenant d une étude observationnelle N = 334 patients atteints de SA ont fait l objet d une surveillance prospective dans le cadre d une étude observationnelle et se sont soumis à au moins 2 examens radiographiques, à au moins 1,5 an d intervalle Utilisation des anti-tnf Tabagisme (paquets-années) VS initiale Score SASSS modifié initial Indice AINS Indice BASDAI initial HLA-B27 Durée de la maladie Sexe (homme p/r à femme) Âge de l apparition 0,52 (0,30-0,88) 1,06 (1,02-1,09) 1,02 (1,01-1,04) 1,07 (1,05-1,09) L instauration précoce d un traitement par des anti-tnfs (durée des symptômes jusqu à 10 ans) et le traitement à long terme (4 ans ou plus) ont été associés à un retard de la progression radiographique rachidienne Haroon N et al. Arthritis Rheum 2013;65: Machado P. Arthritis Rheum 2013;65: Rapport de cotes (IC à 95 %) pour la progression rachidienne radiographique (Aggravation du score SASSS modifié 1 point par année)

22 Discussion Exis%ng classifica%on criteria not sensi%ve enough Many features of AS and PsA not taken into account for diagnosis and/or treatment (enthesi3s, uvei3s ), especially for pa3ents with less than bilateral grade 2 sacroili3s iden3fied by X- ray Exis%ng classifica%on criteria not specific enough Conflict about pa3ents with axial involvement and psoriasis : AS with psoriasis or axial PsA?

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24 Deodhar. Clin Rheumatol 2014;33: Diagnos%c and Classifica%on Criteria Diagnos%c Criteria Used by an MD to make a dgsis When making the dgsis the pretest P depends on the prevalence of the disease The purpose of the dgsis criteria is to help diagnose individual pts Should have a high sensi3vity to iden3fy as many pts as possible Should allow flexibility in diagnos3c confidence Applies to the individual pt Classifica%on Criteria Need to be applied to pts in whom the dgsis has already been made Prevalence of the disease is not important, since all the pts should have the disease Is to iden3fy for researchers homogeneous groups of pts, which facilitates clinical or experimental studies Should have a high specificity to avoid any misclassifica3on Gives a dichotomous yes or no answer Applies to group of pts Dgsis: diagnosis

25 Discussion Hypothesis for the difference Different evolu3on/disease in women vs men Pa3ents involved in the registry suffer from spondylarthri3s rather than SA Unanswered ques3ons Criteria used for the diagnos3c Radiographic status MRI

26 Acknowledgments BIOTRAC Inves3gators JSS Medical Research Sponsor: Janssen Canada

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34 DATA From The DESIR Cohort Objectives: To inves3gate the longitudinal rela3onship between inflammatory lesions in sacroiliac joints on MRI (MRI- SI) and clinical disease ac3vity measures (DA) in pa3ents with axial spondyloarthri3s (axspa). Methods: The rela3onship between MRI- SI (as dependent variable) and disease ac3vity (ASDAS, BASDAI, pa3ent's global DA, night pain, CRP and erythrocyte sedimenta3on rate) as independent variables, was inves3gated using two types of generalised es3ma3ng equa3ons (GEE) models* Arer 2- year follow up, data from 167 pa3ents (50% males) fulfilling the AxSpA criteria: In male pa3ents, but not in female pa3ents, with axspa, clinical DA, especially if measured by ASDAS, is longitudinally associated with MRI- SI inflammatory lesions 1. *model of absolute scores and model of change scores. 1- Navarro- ompan V, Ann Rheum Dis, 75(5):874-8, 2016

35 Baseline Characteris%cs of The DESIR Cohort Pa3ents were enrolled (inclusion period 2007 to April 2010) if they were aged > 18 years and <50 years and suffering from back pain involving the thoracic, lumbar spine or bubock area from more than 3 months less than 3 years. Such back pain had to fulfil the characteris3cs of inflammatory in accordance to either the Berlin or the Calin criteria. Dougados M, Joint Bone Spine 82, , 2015