| Abstract
| - Background. Previous analyses suggested that the HLA-DRB1 shared epitope (SE), and the IL4R V50I and the FcγRIIb I232T single nucleotide polymorphisms (SNPs) affected response to adalimumab (ADA) plus methotrexate (MTX)1. Their effect on long-term responses is unclear. Objectives. To examine 78-wk clinical responses according to 3 candidate loci: HLA-DRB1 SE, and IL4R I50V and FcγRIIb I232T SNPs. Methods. MTX-naïve patients (pts) ≥18 yr with RA <1 yr, active disease [DAS28 (CRP)>3.2, ESR≥28 mm/hr or CRP≥1.5 mg/dL], and >1 erosion, RF+, or anti-CCP+ were randomized to ADA+MTX or placebo (PBO)+MTX for 26 wks (Period 1, P1). Pts who achieved a stable LDA target (DAS28<3.2 at wks 22 & 26) with ADA+MTX were re-randomized to continue ADA+MTX or have ADA blindly withdrawn for 52 wks (P2). Pts who achieved the target with PBO+MTX continued blinded therapy. Pts who did not achieve the target were offered open-label (OL) ADA+MTX. Results. Baseline demographics were similar across alleles. The table shows the percentage of pts achieving DAS28<3.2 at wk 78. There were no consistent patterns for the IL4R alleles in any group. While limited by small sample sizes, pts with FcγRIIb-CC appeared to have higher responses at wk 78 among groups initially exposed to ADA+MTX during P1. The positive influence of SE was apparent at wk 78 in groups originally exposed to ADA+MTX, particularly in pts who did not achieve the stable LDA target at wks 22 & 26 but continued ADA+MTX. However, this pattern was not observed in pts who failed to achieve the target with MTX and were subsequently treated with ADA+MTX. The interaction between SE and IL4R observed during P1 was not apparent in long-term responses to ADA+MTX. Percentage of Pts with DAS28<3.2 at Week 78, n/N (%), non-responder imputationTreatmentHLA-DRB1 SEIL4RFcγRIIbPeriod 1Period 20x1x2xAAAGGGTTTCCCPBO+MTXPBO+MTX30/ 40 (75.0)25/ 38 (65.8)10/ 15 (66.7)18/ 24 (75.0)31/ 44 (70.5)16/ 25 (64.0)47/ 69 (68.1)18/ 24 (75.0)0/ 0 (0)OL ADA+MTX59/115 (51.3)80/148 (54.1)19/ 42 (45.2)49/ 93 (52.7)83/164 (50.6)26/ 48 (54.2)117/225 (52.0)40/ 76 (52.6)1/ 4 (25.0)ADA+MTXPBO+MTX21/ 28 (75.0)25/ 36 (69.4)17/ 22 (77.3)23/ 31 (74.2)33/ 44 (75.0)7/ 11 (63.6)43/ 63 (68.3)17/ 20 (85.0)3/ 3 (100)ADA+MTX16/ 22 (72.7)36/ 45 (80.0)18/ 20 (90.0)23/ 31 (74.2)33/ 39 (84.6)14/ 17 (82.4)54/ 67 (80.6)14/ 18 (77.8)2 2/ 2 (100)OL ADA+MTX29/ 81 (35.8)49/113 (43.4)18/ 36 (50.0)28/ 68 (41.2)49/109 (45.0)19/ 53 (35.8)87/200 (43.5)8/ 29 (27.6)1/ 1 (100) Conclusions. Regardless of genetic background, wk 78 responses were generally higher for pts who achieved the stable LDA target at wks 22 & 26. The positive effects of HLA-DRB1 SE and FcγRIIb-CC in response to ADA+MTX previously noted at wk 26 were less apparent at wk 78, but noticeable in pts who failed to achieve the target. Further, while SE predicted clinical response to ADA+MTX, particularly when combined with IL4R alleles, it had no influence on the ability to withdraw ADA in pts who achieved LDA. These findings may indicate that genetic factors have a stronger influence on initial treatment response than on sustained disease control. References. Skapenko et al. EULAR 2011 #THU0309. Disclosure of Interest. A. Skapenko: None Declared, J. Smolen Grant/Research support from: Abbott, Amgen, Astra-Zeneca, BMS, Celgene Centocor-Janssen, Glaxo, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB, Consultant for: Abbott, Amgen, Astra-Zeneca, BMS, Celgene Centocor-Janssen, Glaxo, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB, A. Kavanaugh Grant/Research support from: Abbott, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, Consultant for: Abbott, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, S. Santra Shareholder of: Abbott, Employee of: Abbott, H. Kupper Shareholder of: Abbott, Employee of: Abbott, H. Schulze-Koops Consultant for: Abbott
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