PMID- 34537057 OWN - NLM STAT- MEDLINE DCOM- 20211028 LR - 20211028 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 23 IP - 1 DP - 2021 Sep 18 TI - HLA-DRB1 risk alleles for RA are associated with differential clinical responsiveness to abatacept and adalimumab: data from a head-to-head, randomized, single-blind study in autoantibody-positive early RA. PG - 245 LID - 10.1186/s13075-021-02607-7 [doi] LID - 245 AB - BACKGROUND: Certain risk alleles associated with autoantibody-positive rheumatoid arthritis (RA) have been linked to poorer prognoses. In patients with autoantibody-positive RA, abatacept shows differential efficacy to tumor necrosis factor inhibitors. Our aim was to investigate the relationship between clinical response to abatacept and to adalimumab and presence of risk alleles encoding human leukocyte antigen (HLA)-DRB1 shared epitope (SE) in RA. METHODS: In this head-to-head study, biologic-naive adults with early (/= 1 SE allele) or SE-negative (no SE alleles). Efficacy was assessed at weeks 24 and 48. RESULTS: Forty patients each received abatacept (9 SE-negative, 30 SE-positive, one unknown) or adalimumab (9 SE-negative, 31 SE-positive). Mean age and disease duration were 46.0 years and 5.5 months, respectively. At week 24, a greater percentage of abatacept patients achieved 50% improvement in ACR criteria (ACR50) compared with adalimumab patients (73% vs 45%, respectively) and estimate of difference (95% confidence interval [CI]), 28 (5, 48). In SE-positive patients, ACR50 estimate of difference (95% CI) was 32 (7, 55). During the open-label period, responses were sustained in the abatacept non-switch group and showed trends toward further improvement in the adalimumab-to-abatacept switch group at week 48, in both the overall and the SE-positive subpopulation. No new safety signals were identified. CONCLUSIONS: In MTX-IR patients with early, autoantibody-positive RA, abatacept resulted in numerically higher efficacy responses versus adalimumab after 24 weeks, with more pronounced treatment differences in SE-positive patients. After 48 weeks, responses were sustained in patients who continued abatacept while those who switched to abatacept showed further clinical improvement, overall, and in SE-positive patients. This supports co-stimulation blockade as an effective treatment strategy for patients with early, autoantibody-positive RA, particularly among SE-positive patients. TRIAL REGISTRATION: NIH US National Library of Medicine, NCT02557100 . Registered on September 23, 2015. CI - (c) 2021. The Author(s). FAU - Rigby, William AU - Rigby W AD - Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr, Lebanon, NH, 03766, USA. FAU - Buckner, Jane H AU - Buckner JH AD - Benaroya Research Institute at Virginia Mason, 1201 9th Ave, Seattle, WA, 98101, USA. FAU - Louis Bridges, S Jr AU - Louis Bridges S Jr AD - Division of Rheumatology, Hospital for Special Surgery, 535 E 70th St, New York, NY, 10021, USA. FAU - Nys, Marleen AU - Nys M AD - Bristol Myers Squibb, Avenue de Finlande 4, 1420, Braine-I'Alleud, Belgium. FAU - Gao, Sheng AU - Gao S AD - Bristol Myers Squibb, 3401 Princeton Pike, Princeton, NJ, 08648, USA. FAU - Polinsky, Martin AU - Polinsky M AD - Bristol Myers Squibb, 3401 Princeton Pike, Princeton, NJ, 08648, USA. FAU - Ray, Neelanjana AU - Ray N AD - Bristol Myers Squibb, 3401 Princeton Pike, Princeton, NJ, 08648, USA. FAU - Bykerk, Vivian AU - Bykerk V AUID- ORCID: 0000-0002-1219-3845 AD - Division of Rheumatology, Hospital for Special Surgery, 535 E 70th St, New York, NY, 10021, USA. bykerkv@hss.edu. LA - eng SI - ClinicalTrials.gov/NCT02557100 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210918 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (Antirheumatic Agents) RN - 0 (HLA-DRB1 Chains) RN - 7D0YB67S97 (Abatacept) RN - FYS6T7F842 (Adalimumab) SB - IM MH - Abatacept/therapeutic use MH - Adalimumab/therapeutic use MH - Adult MH - Alleles MH - *Antirheumatic Agents/therapeutic use MH - *Arthritis, Rheumatoid/drug therapy/genetics MH - HLA-DRB1 Chains/genetics MH - Humans MH - Single-Blind Method PMC - PMC8449494 OTO - NOTNLM OT - Abatacept OT - Adalimumab OT - Anti-citrullinated protein antibodies OT - Arthritis, rheumatoid OT - Biological therapy OT - Therapeutics COIS- WR has acted as a consultant for AbbVie, Bristol Myers Squibb, Genentech, Gilead, and Pfizer. JB was a paid consultant for Eli Lilly, is on the advisory board of GentiBio, and received grant/research support from Bristol Myers Squibb, Eli Lilly, Janssen, Novo Nordisk, and Pfizer. SLB has nothing to declare. MN, SG, MP, and NR are shareholders in and employees of Bristol Myers Squibb. VB received grant/research support (paid to institution) from Amgen, Bristol Myers Squibb, the Cedar Hill Foundation, and the NIH; consulting fees from Bristol Myers Squibb; and financial support from Amgen, Bristol Myers Squibb, Gilead, Pfizer, and UCB. EDAT- 2021/09/20 06:00 MHDA- 2021/10/29 06:00 PMCR- 2021/09/18 CRDT- 2021/09/19 20:21 PHST- 2021/04/08 00:00 [received] PHST- 2021/08/14 00:00 [accepted] PHST- 2021/09/19 20:21 [entrez] PHST- 2021/09/20 06:00 [pubmed] PHST- 2021/10/29 06:00 [medline] PHST- 2021/09/18 00:00 [pmc-release] AID - 10.1186/s13075-021-02607-7 [pii] AID - 2607 [pii] AID - 10.1186/s13075-021-02607-7 [doi] PST - epublish SO - Arthritis Res Ther. 2021 Sep 18;23(1):245. doi: 10.1186/s13075-021-02607-7.