Abstract Objective To perform a large‐scale association analysis of single‐nucleotide polymorphisms (SNPs) in patients with radiographically defined osteoarthritis (OA) of the knee. Methods We examined >25,000 SNPs located within ∼14,000 genes for associations with radiographically defined knee OA, using polymerase chain reaction and MassExtend amplification techniques. Allele frequencies were estimated initially in DNA pools from 335 female patients with knee OA and 335 asymptomatic and radiographically negative female control subjects. All were of northern European ancestry. Significant allele frequency differences were validated by genotyping of individual DNA samples. Confirmed significant findings were verified in 2 additional case–control samples from the UK (443 cases and 303 controls) and Newfoundland (346 cases and 264 controls). Chondrosarcoma cell lines were used to test for potential differences in gene expression. Results The marker most strongly associated with the risk of knee OA was rs912428, a C/T polymorphism in intron 1 of LRCH1 , a gene on chromosome 13q14 that encodes a novel protein of as‐yet‐unknown function. The frequency of the T allele compared with controls was consistently increased by 40% across all 3 case–control groups. Additional subanalyses in case–control samples with hip OA and hand OA suggested similar trends, but did not reach statistical significance. Association fine‐mapping using 10 additional SNPs in LRCH1 confirmed intron 1 as the region of highest association but failed to reveal variations with significance stronger than the marker SNP, as did the haplotype analysis. LRCH1 was not up‐regulated or overexpressed in chondrosarcoma cell lines exposed to inflammatory stimuli, suggesting a possible structural role. Conclusion A genetic variant in LRCH1 was consistently associated with knee OA in 3 samples from 2 populations. Our results also suggest that the same association with OA may exist at other sites. Additional genetic and experimental work is needed to elucidate the precise mechanism by which the LRCH1 gene influences OA risk.
Up to one third of total joint replacement patients (TJR) experience poor surgical outcome.To identify metabolomic signatures for non-responders to TJR in primary osteoarthritis (OA) patients.A newly developed differential correlation network analysis method was applied to our previously published metabolomic dataset to identify metabolomic network signatures for non-responders to TJR.Differential correlation networks involving 12 metabolites and 23 metabolites were identified for pain non-responders and function non-responders, respectively.The differential networks suggest that inflammation, muscle breakdown, wound healing, and metabolic syndrome may all play roles in TJR response, warranting further investigation.
To evaluate the effect of ustekinumab (UST), an IL-12/23 p40 inhibitor, on inhibition of progression of structural damage in patients with active psoriatic arthritis (PsA) at wk24 and wk52 in the PSUMMIT 1 and PSUMMIT 2 trials.
Methods
Adult PsA patients with active disease (≥5 SJC and ≥5 TJC; CRP≥0.3mg/dL [ULN 1.0 mg/dL]) despite DMARD and/or NSAID therapy (PSUMMIT 1, n=615; PSUMMIT 2, n=132) or previously treated with DMARD and/or NSAID, and prior anti-TNFα therapy (PSUMMIT 2, n=180) were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks, thereafter. At wk16, patients with <5% improvement in TJC & SJC entered blinded early escape [EE] (PBO$→ $UST45mg; UST45mg$→ $90mg; 90mg$→ $90mg). No concomitant DMARDs with the exception of MTX (approximately 50% of patients in each study) were permitted. Radiographs of hands and feet were taken at wks 0, 24, and 52 regardless of EE status, or at the time of study drug discontinuation (unless radiographs were completed within the prior 8wks). Erosions and joint space narrowing (JSN) were evaluated by independent readers blinded to treatment, patient IDs and image time sequence using PsA modified van der Heijde-Sharp (vdH-S) method (total score ranging from 0-528). The major secondary endpoint of change from baseline in total vdH-S scores at wk24 was analyzed based on a pre-specified integrated data analysis using data combined from both studies. Imputation of missing data was done using linear extrapolation or median change of 0.
Results
Baseline disease characteristics including total vdH-S, TJC, SJC and CRP were comparable between PSUMMIT 1 & 2. In the integrated analyses, both UST 45 mg and 90 mg treated patients demonstrated a significant difference in change from baseline in total vdH-S scores at wk24 vs PBO (Table). Moreover, continued inhibition was demonstrated through wk 52; patients randomized to PBO who initiated UST at wk16 or 24 demonstrated slowing of radiographic progression by wk52 (mean change in total vdH-S wk24 to wk52 of 0.08). These observations were reproduced when PSUMMIT 1 was evaluated alone. In PSUMMIT 2, a demonstrable effect of UST on inhibition of structural damage progression could not be discerned; these results may have been impacted by missing radiographic data, especially among PBO-treated patients (23% missing radiographs).
Conclusions
Based upon the pre-specified integrated data analysis, ustekinumab inhibits radiographic progression at wk24.
Disclosure of Interest
I. McInnes Grant/research support: Abbott, BMS, Janssen, Pfizer, Roche, Merck/Schering-Plough, and UCB., C. Ritchlin Grant/research support: Amgen, Janssen, and UCB., Consultant for: Abbott, Amgen, Janssen, Regeneron, Roche, and UCB., P. Rahman Grant/research support: Abbott, Amgen, Janssen, Merck/Schering-Plough, and Wyeth., L. Puig Grant/research support: Abbott, Amgen, Celgene, Janssen, Merck/Schering-Plough, and Pfizer., A. Gottlieb Grant/research support: Amgen, Abbott, Celgene, Immune Control, Janssen, Lilly, Novartis, Novo Nordisk, Pfizer, and UCB., Consultant for: Abbott, Actelion, Amgen,Astellas, Belersdorf, BMS, Canfite, Celgene, DemiPsor, Incyte, Janssen, Lilly ICOS, Merck, Novartis, Novo Nordisk, Pfizer, Teva, and UCB., M. Song Employee of: Janssen Research & Development, LLC, B. Randazzo Employee of: Janssen Research & Development, LLC, S. Li Employee of: Janssen Research & Development, LLC, Y. Wang Employee of: Janssen Research & Development, LLC, A. Mendelsohn Employee of: Janssen Research & Development, LLC, A. Kavanaugh Grant/research support: Abbott, Amgen, Janssen, and UCB.
Adalimumab (ADA) is indicated for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Peripheral arthritis, enthesitis, and dactylitis are important features in patients (pts) suffering from spondyloarthritis (SpA). Pts with peripheral SpA not diagnosed with PsA or AS (non-PsA, non-AS) may also benefit from anti-TNF therapy. ABILITY 2 is the first randomized controlled trial to use the ASAS peripheral SpA criteria.1
Objectives
To evaluate efficacy and safety of ADA in pts with non-PsA, non-AS 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 to NSAIDs. Pts were randomized 1:1 to ADA 40 mg every other wk or placebo (PBO) for 12 wks followed by a 92-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) from baseline (BL) in Patient Global Assessment of Disease Activity (PGA) and PGA-pain and ≥40% improvement in ≥1 of the following: SJC and TJC; Enthesitis Count, or Dactylitis Count. Other outcomes included Physician Global Assessment (PhGA), BASDAI, enthesitis indices, HAQ-S, and SF-36v2. Adverse events (AE) were collected throughout the study.
Results
165 pts were randomized, 84/81, ADA/PBO. BL demographics/disease characteristics were similar between groups, except mean age was higher (43/39 yrs) and % pts with dactylitis count>0 was lower (16/30) in the ADA group. At BL, 99% of pts had TJC>0, 93% had SJC>0, and 87% had enthesitis count>0. At Wk 12, the proportion of ADA pts achieving PSpARC 40 was higher vs. PBO (P=.006) (table). Overall, mean improvement in 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.
Conclusions
Adalimumab significantly improved signs, symptoms, and physical function of pts with active non-PsA, non-AS peripheral SpA and was well-tolerated. ABILITY 2 results suggest that ADA can be a treatment option for peripheral SpA pts with inadequate response to NSAIDs.
References
Rudwaleit M, et al. Ann Rheum Dis 2011;70:25-31.
Disclosure of Interest
P. Mease Grant/Research support from: Abbott, Consultant for: Abbott, Speakers Bureau: Abbott, J. Sieper Grant/Research support from: Abbott, Merck, Pfizer, UCB, Consultant for: Abbott, Merck, Pfizer, UCB, Speakers Bureau: Abbott, Merck, Pfizer, UCB, F. Van den Bosch Grant/Research support from: Abbott, Merck, UCB, Speakers Bureau: Abbott, Merck, P. Rahman Grant/Research support from: Janssen, Schering, Consultant for: Abbott, Amgen, Janssen, Roche, Schering, Speakers Bureau: Abbott, Amgen, Janssen, Schering, BMS, K. Obermeyer Shareholder of: Abbott, Employee of: Abbott, A. Pangan Shareholder of: Abbott, Employee of: Abbott
Abstract Objectives To evaluate the association between enthesitis resolution (ER) and dactylitis resolution (DR) and meaningful improvements in patient-reported outcomes (PROs) among biologic-naïve patients with PsA receiving guselkumab in the DISCOVER-2 study. Methods Enthesitis and dactylitis, characteristic lesions of PsA, were evaluated by independent assessors using the Leeds Enthesitis Index (range, 0–6) and Dactylitis Severity Score (range, 0–60). Proportions of patients with ER or DR (score = 0) among those with score > 0 at baseline were determined at weeks 24, 52, and 100. PROs included: fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), pain (0–100 visual analog scale), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and health-related quality of life (36-item Short-Form Health Survey physical/mental component summary [SF-36 PCS/MCS]). Meaningful responses were defined as: improvements of ≥ 4 for FACIT-Fatigue, ≥ 0.35 for HAQ-DI, and ≥ 5 for SF-36 PCS/MCS and absolute scores of ≤ 15 for minimal pain and ≤ 0.5 for normalized HAQ-DI. Associations between ER/DR status and PRO response status were tested using a Chi-square test. Results Guselkumab-treated patients with ER were more likely than those without ER to achieve minimal pain ( p < 0.001), normalized HAQ-DI ( p < 0.001), and PCS response ( p < 0.05) at weeks 24, 52, and 100. Patients with DR were more likely than those without DR to achieve FACIT-Fatigue response at week 24 and week 52 (both p ≤ 0.01) and minimal pain at week 24 and normalized HAQ-DI at week 52 (both p ≤ 0.03). Conclusion In biologic-naïve patients with active PsA treated with guselkumab, achieving ER or DR was associated with durable improvements in selected PROs, including those of high importance to patients. Trial registration ClinicalTrials.gov ( https://clinicaltrials.gov ) NCT03158285; Registered: May 16, 2017. Key Points • At week 100, 65% and 76% of guselkumab-treated patients achieved enthesitis and dactylitis resolution (ER/DR). • Achieving ER was associated with achieving DR and vice versa through the end of study. • Achieving ER or DR was associated with durable and meaningful improvements in selected patient-reported outcomes.
To examine the impact of ustekinumab (UST) treatment on patient reported outcomes in patients with active psoriatic arthritis (PsA) using week 24 data from two Phase 3 clinical studies, PSUMMIT I and II.
Methods
Adult patients with active PsA despite DMARD and/or NSAID therapy (PSUMMIT I, n=617) or previously treated with anti-TNFα therapy (PSUMMIT II, n=312) were randomized to receive UST 45mg, 90mg, or placebo (PBO) at wks 0, 4, and q12wks, thereafter. Patient reported outcomes were measured using the Health Assessment Questionnaire (HAQ), Dermatology Quality Life Index (DLQI), SF-36health survey questionnaire (SF-36), Visual Analogue Scales (VAS) for impact of PsA on work productivity (0-10), patient assessment of pain (0-10), and disease activity (0-10). Sub-analyses were conducted by combining both studies into 3 mutually exclusive groups based on treatment history: MTX naïve, previously treated with MTX therapy, and previously treated with anti-TNF therapy.
Results
At baseline, patients in both studies had moderate to severe physical disability and impaired health related quality of life with a mean HAQ score of ≥1.25, mean DLQI score of ≥10 and mean SF-36 PCS and MCS below 50 (normal population score). In PSUMMIT I, UST-treated patients achieved statistically significantly greater improvements in HAQ (- 0.31 and -0.4 vs. -0.1), DLQI (-6.6 and -7.5 vs. -1.4), and SF-36 PCS (4.9 and 6.2 vs. 1.4), for the UST 45mg, 90mg, vs. PBO groups, respectively. When compared to PBO, greater proportions of UST-treated patients achieved clinical meaningful improvements in HAQ (≥0.3) (47.8% and 47.5% vs. 28.2%), DLQI (≥5) (58.6% and 63.1% vs. 32.9%), and SF-36 PCS (≥5) (45.5%, and 53.3% vs. 26.0%), for the UST 45mg, 90mg, vs. PBO groups, respectively. Similar results were observed in PSUMMIT II and in the sub-analyses by MTX naïve, prior MTX experienced, and prior anti-TNFα experienced patients. Similar results were also observed in SF-36 sub-scales, especially in bodily pain and physical health. In the anti-TNF naïve population, statistically significantly greater improvement in SF-36 MCS was observed in the combined UST 45mg and 90mg group vs PBO Additionally, UST-treated patients achieved statistically significantly greater improvements in patient assessment of pain, patient assessment of disease activity, and greater reduction in impact of disease on work productivity vs PBO-treated patients.
Conclusions
UST improves physical function, improves general, arthritis and skin-related quality of life, and reduces the impact of disease on work productivity in patients with active PsA regardless of current or prior MTX use or prior anti-TNF experience.
Disclosure of Interest
P. Rahman Grant/research support from: Janssen R&D, LLC, L. Puig Grant/research support from: Janssen R&D, LLC, A. Gottlieb Grant/research support from: Janssen R&D, LLC, A. Kavanaugh Grant/research support from: Janssen R&D, LLC, I. McInnes Grant/research support from: Janssen R&D, LLC, C. Ritchlin Grant/research support from: Janssen R&D, LLC, S. Li Shareholder of: Johnson& Johnson, Employee of: Janssen R&D, LLC, Y. Wang Shareholder of: Johnson& Johnson, Employee of: Janssen R&D, LLC, N. Zhao Shareholder of: Johnson& Johnson, Employee of: Janssen Global Services, LLC, R. Ganguly Shareholder of: Johnson& Johnson, Employee of: Janssen Global Services, LLC, M. Song Shareholder of: Johnson& Johnson, Employee of: Janssen R&D, LLC, C. Han Shareholder of: Johnson& Johnson, Employee of: Janssen Global Services, LLC
The objective of this study is to report long-term, end-of-study-program safety outcomes, relating to major adverse cardiovascular events (MACE), in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (AxSpA) who received ≥1 dose of Ixekizumab (IXE) over 5 years (PsO) or 3 years (PsA, axSpA).
Methods
The incidence of MACE was assessed across 25 randomized clinical trials (17 PsO, 4 PsA, 4 axSpA) examining long-term safety of IXE. MACE rates were analyzed for pooled studies by years of therapy, through March 2022. Exposure-adjusted incidence rates (IRs) per 100 patient-years, at successive year intervals are reported.
Results
The incidence of MACE was low among patients with PsO (IR=0.5), PsA (IR=0.5), and axSpA (IR=0.3). In the PsO cohort, of the 103 reported MACE cases, 20 were fatal (19.4%), 57 recovered (55.3%), and 17 recovered with sequelae (16.5%). Of the 12 reported MACE cases in the PsA cohort, 2 were fatal (16.7%), 9 recovered (75.0%), and 1 recovered with sequelae (8.3%). All 6 MACE cases reported in the axSpA cohort recovered (100.0%). IRs were low and stable over the treatment periods. The most common types of MACE reported in the PsO, PsA and axSpA cohorts were non-fatal myocardial infarction (PsO: IR= 0.3; PsA: IR=0.3; axSpA: IR=0.3), nonfatal stroke (PsO: IR=0.1; PsA: IR=0.2) and vascular death (PsO: IR=0.1; PsA: IR=0.1). All MACE cases were confirmed by adjudication.
Conclusion
The incidence of MACE was low and stable over the IXE treatment periods examined.
REFERENCES:
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Acknowledgements:
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Disclosure of Interests
Mark Lebwohl Consultant of: Arcutis, Boehringer Ingelheim, Bristol Myers. Squibb, Verrica, AbbVie, Amgen, Eli Lilly, Janssen, Ortho Dermatologics, Pfizer, UCB Pharma, Avotres Therapeutics, AnaptysBio, Aristea Therapeutics, BioMX, Cara Therapeutics, Castle Biosciences, Dermavant, Evommune, Facilitatation of International Dermatology Education, Forte. Biosciences, Foundation for Research and Education in Dermatology, Hexima, Meiji Seika Pharma, Mindera Health, Regeneron, Seanergy, Incyte, Arrive Technologies, Dr Reddy's Laboratories, Evelo Biosciences, Helsinn Therapeutics, LEO Pharma, Mount Sinai, CorEvitas (formerly Corrona), Grant/research support from: Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara. Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development, LLC, Novartis, Ortho Dermatologics, Regeneron, and UCB, Inc., Atul Deodhar Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, UCB Pharma, Aurinia, Moonlake, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB, Sergio Schwartzman Speakers bureau: AbbVie, Janssen, Lilly, Pfizer, Novartis, UCB, Consultant of: AbbVie, Janssen, Eli Lilly and Company, Pfizer, Novartis, UCB, Myriad, Regeneron, Sanofi, Stelexis, Jubilant, Teijin, National Psoriasis Foundation Medical Boar, Grant/research support from: Lilly, Carlo Salvarani Consultant of: AbbVie, Eli Lilly and Company, and Roche, Grant/research support from: Roche, Meghan Feely Shareholder of: Eli Lilly and Company, Speakers bureau: Mount Sinai, Consultant of: Mount Sinai, Hospital, NY, Eli Lilly and Company, Aerolase, Castle Biosciences, Galderma Aesthetics, Revian, Sonoma Pharmaceuticals, Suneva Medical, and Sun Pharmaceutical Industries, AAD Investment Committee, AAD Media Expert Team, AEI Leadership Network, Leonine Forum, WDS Committees: Practice Advisory, Finance and Investment, Fundraising and Philanthropic Activities, Prevention Medical Review Board, ASDS Social Media Ambassador, Grant/research support from: Eli Lilly and Company, Mount Sinai, MC Medical Group, The Dermatology and Laser Group, Windsor Dermatology, Employee of: Eli Lilly and Company, Danting Zhu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Proton Rahman Consultant of: AbbVie, Eli Lilly and Company, Janssen, Novartis, and Pfizer, Grant/research support from: Janssen and Novartis, Kim Papp Speakers bureau: AbbVie, Amgen, Bausch Health/Valeant, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Merck, Novartis, Pfizer, Sanofi, Consultant of: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv. Therapeutics, Xencor, Grant/research support from: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv. Therapeutics, Xencor, Joseph F. Merola Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi Regeneron, Sun Pharma, and UCB Pharma, Alice B Gottlieb Shareholder of: Xbiotech (stock options for an RA project), Consultant of: Amgen, AnaptysBio, Avotres Therapeutics, Boehringer. Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Xbiotech, Grant/research support from: AnaptysBio, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, BMS, and UCB Pharma, Andrew Blauvelt Speakers bureau: AbbVie, UCB, Consultant of: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, EcoR1, Vibliome, Grant/research support from: AbbVie, Acelyrin, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Evelo, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma Investigator (payments made to my company),
Epidemiological studies have established a large recurrence risk ratio among siblings suggesting a strong genetic component for psoriasis and psoriatic arthritis (1). Better understanding of the heritability of PsC, PsV and PsA will lead to more efficient genetic profiling for psoriatic disease.
Objectives
We set out to assess the heritability of cutaneous psoriasis without known arthritis (PsC); psoriasis vulgaris (psoriasis irrespective of arthritis, PsV) and psoriatic arthritis (PsA) by interrogating SNPs from a large scale genotyping array.
Methods
The heritability of PsC, PsV and PsA were estimated by interrogating 715 PsA, 1155 PsC, 2938 PsV patients and 3117 unaffected controls of European ancestry. The samples were genotyped on a custom Axiom Biobank plus genotyping array and core GWAS chip with 461,092 autosomal SNPs. Further imputation led to 1.3M well-imputed SNPs based on the autosomal reference panel of the HapMap Phase 3 (HM3) CEU cohort. After strict filtering, 230k autosomal SNPs without imputation and 401k autosomal SNPs after imputation were retained for heritability estimation. The following two methods were used to determine the heritability of PsC, PsV and PsA from SNP based data: Linkage Disequilibrium Adjusted Kinships (LDAK) and GCTA which relies on the restricted maximum likelihood algorithm (ReML). Sex and the top 5 principal components were used as covariates to control for gender effect and population stratification in each analysis. Parallel analyses were performed after removing SNPs from the MHC region. The prevalence also was used to adjust the heritability estimation.
Results
The heritability assessment for psoriatic disease for each method is presented in the table with and without imputation. Although the heritability estimates vary depending on the method, the heritability of PsC appears to be greater than PsA, for analysis that was done with and without imputation. Similar trends are noted when non-MHC SNPs were assessed.
Conclusion
SNP based heritability estimates suggest greater heritability for PsC as compared to PsA. Common environmental factors may need to be considered to account the strong recurrence rate of PsA over psoriasis among first degree relatives reported in previous epidemiological studies, as this finding is not noted from large SNP based association studies.
References
[1] Chandran V, Schentag CT, Brockbank JE, Pellett FJ, Shaumugrajah S, Toloza SM, Rahman P, Gladman DD. Familial aggregation of psoriatic arthritis. Ann Rheum Dis. 2009; 68(5):664-7.
Disclosure of Interests
Quan Li: None declared, Vinod Chandran: None declared, Lam Tsoi: None declared, Rajan Nair: None declared, Dafna D Gladman Grant/research support from: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, James T. Elder: None declared, Proton Rahman: None declared
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