ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 3195

Circulating Micro-RNA Profiles in Responders to Adalimumab Plus Methotrexate Versus Methotrexate Alone: A Placebo-Controlled Clinical Trial

Jacob Sode1,2,3, Sophine B. Krintel4, Anting L. Carlsen5, Merete Lund Hetland6, Julia Johansen7,8, Kim Hørslev-Petersen9, Kristian Stengaard-Pedersen10, Peter Junker11, Mikkel Østergaard12,13, Niels H. H. Heegaard14,15 and OPERA study group, 1Department of Autoimmunology and Biomarkers, Statens Serum Institut, Copenhagen, Denmark, 2Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark, 3Department of Rheumatology, Frederiksberg Hospital, Frederiksberg, Denmark, 4Department of Rheumatology, Copenhagen University Hospital at Glostrup, Copenhagen, Denmark, 5Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark, 6The DANBIO Registry, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, 7Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark, 8Departments of Medicine and Oncology, Copenhagen University Hospital at Herlev, Copenhagen, Denmark, 9Rheumatology, Research Unit at King Christian X Hospital for Rheumatic Diseases, Graasten, Graasten, Denmark, 10Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark, 11Department of Rheumatology, Odense University Hospital, Odense, Denmark, 12Rigshospitalet-Glostrup, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, Glostrup, Denmark, 13Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark, 14Department of Autoimmunology & Biomarkers, Statens Serum Institut, Copenhagen, Denmark, 15Department of Clinical Biochemistry & Pharmacology, Odense University Hospital, Odense C, Denmark

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ,

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy VI: Strategies

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose:

The variable response to anti-TNF therapy in patients with rheumatoid arthritis (RA) remains largely unexplained, and biomarkers for treatment response are scarce. We previously investigated whole blood micro-RNA (miRNA) as predictors of anti-TNF response. In this study we aimed to investigate association between plasma miRNAs and treatment response in 180 DMARD naïve early RA patients enrolled in the OPERA Study, a prospective, double-blinded, placebo-controlled study.

Methods:

Patients were randomized to methotrexate, intra-articular glucocorticoids plus either adalimumab or placebo. All patients had RA (ACR 1987 criteria). Plasma samples for total RNA purification were collected pre-treatment and at 3-month. 91 specific miRNAs were investigated by quantitative RT-PCR on a microfluidic dynamic array. Cq values were normalized with spiked-in synthetic miRNAs and further normalized using means of all endogenous expressed miRNAs. Means were compared (Welch’s t-test) of pre-treatment miRNAs and of the 3-month change in miRNA expression for the groups of responding and non-responding patients. Response was defined by 12-month ACR/EULAR Boolean remission.

Results:

We successfully profiled 76/91 miRNAs in 180 pre-treatment samples and in 170 (94%) 3-month samples. Pre-treatment expression of six miRNAs (Table 1), and altered change in expression of eight miRNAs (Table 2) were associated (p<0.05) with remission to adalimumab treatment. In the placebo group, pre-treatment expression of 12 miRNAs, and altered change in expression of four miRNAs were associated with remission. Adalimumab treated responders had increased pre-treatment miR-27a-3p (p=0.004), which decreased after 3 months compared to non-responders (p=0.0001). Placebo treated responders had increased miR-27a-3p compared to adalimumab responders (p=0.03). miR-146a decreased (p=0.01) in adalimumab responders vs. non-responders consistent with previous data on miR-146a as a putative marker of disease activity. Placebo responders vs. non-responders did not differ with respect to miR-146a changes. In our previous study of whole blood, miR-23a was also associated with remission in the adalimumab group.

Conclusion:

In this well-characterized cohort we have identified miRNAs predictive of treatment response.  Our results suggest miR-27a-3p as particular promising as both predictor and biomarker of response to adalimumab treatment. The results should be interpreted with some reservation due to the large number of associations investigated, and need validation in independent prospective studies.

Table 1. Pre-treatment expression in remitting RA patients

 

 

 

 

miRNA

Adalimumab + DMARD

 

Placebo + DMARD

 

 

Remission (n=43) vs no-remission (n=43)

p-value

Remission (n=29) vs no- remission (n=54)

p-value

hsa-miR-27a-3p

↑

0.004

–

0.17

hsa-miR-10b-5p

↓

0.006

–

0.11

hsa-miR-23a-3p

↑

0.01

–

0.42

hsa-miR-142-3p

↓

0.01

–

0.52

hsa-miR-27b-3p

↓

0.03

–

0.25

hsa-miR-19b-3p

↑

0.05

–

0.17

hsa-miR-28-3p

–

0.31

↑

0.01

hsa-miR-223-3p

–

0.14

↓

0.01

hsa-miR-145-5p

–

0.50

↓

0.02

hsa-miR-378-3p

–

0.53

↑

0.02

hsa-miR-7-5p

–

0.34

↑

0.03

hsa-miR-15b-5p

–

0.89

↓

0.03

hsa-miR-106a-5p

–

0.18

↓

0.03

hsa-miR-342-3p

–

0.24

↑

0.03

hsa-miR-199a/b-3p

–

0.11

↓

0.03

hsa-miR-208a-3p

–

0.29

↑

0.03

hsa-miR-29c-3p

–

0.11

↓

0.05

hsa-miR-106b-5p

–

0.39

↓

0.05

Table 2. Change in expression in remitting RA patients

 

 

 

 

miRNA

Adalimumab + DMARD

 

Placebo + DMARD

 

 

Remission (n=43) vs. no-remission (n=43)

p-value

Remission (n=29) vs. no- remission (n=54)

p-value

hsa-miR-27a-3p

↓

0.0001

–

0.25

hsa-miR-146a-5p

↓

0.01

–

0.38

hsa-miR-29c-3p

↑

0.02

–

0.90

hsa-miR-24-3p

↓

0.03

–

0.19

hsa-miR-423-5p

↓

0.04

↑

0.01

hsa-miR-21-5p

↓

0.04

–

0.16

hsa-miR-122-5p

↑

0.04

–

0.72

hsa-miR-19b-3p

↓

0.05

–

0.09

hsa-miR-659-3p 

–

0.33

↓

0.03

hsa-miR-10b-5p

–

0.08

↑

0.04

hsa-miR-28-3p 

–

0.09

↓

0.05

Disclosure: J. Sode, None; S. B. Krintel, None; A. L. Carlsen, None; M. Lund Hetland, None; J. Johansen, None; K. Hørslev-Petersen, None; K. Stengaard-Pedersen, None; P. Junker, None; M. Østergaard, None; N. H. H. Heegaard, None.

To cite this abstract in AMA style:

Sode J, Krintel SB, Carlsen AL, Lund Hetland M, Johansen J, Hørslev-Petersen K, Stengaard-Pedersen K, Junker P, Østergaard M, Heegaard NHH. Circulating Micro-RNA Profiles in Responders to Adalimumab Plus Methotrexate Versus Methotrexate Alone: A Placebo-Controlled Clinical Trial [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/circulating-micro-rna-profiles-in-responders-to-adalimumab-plus-methotrexate-versus-methotrexate-alone-a-placebo-controlled-clinical-trial/. Accessed .

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