Effect of a Non Biologic Treat-to-Target Strategy on MRI-Determined Inflammatory and Destructive Changes in Early Rheumatoid Arthritis - Results from a 2-Year Investigator-Initiated Double-Blind Randomized Controlled Clinical Trial

Signe Moller-Bisgaard^1,2, Bo Jannik Ejbjerg², Iris Eshed³, Kim Horslev-Petersen⁴, Merete Lund Hetland⁵, Anne G. Jurik⁶, Jørgen Vallø⁷, Henrik Thomsen⁸, Trine Torfing⁹, Kristian Stengaard-Pedersen¹⁰, Peter Junker¹¹, Niels Steen Krogh¹², Tine Lottenburger¹³, Torkell Ellingsen¹⁴, Lis Smedegaard Andersen¹⁵, Ib Hansen¹⁰, Henrik Skjødt¹⁶, Anders Svendsen¹⁴, Ulrik Tarp¹⁰, Jan Pødenphant¹⁵, Jens Kristian Pedersen⁷, Hanne Lindegaard¹⁴ and Mikkel Østergaard¹, ¹Center for Rheumatology and Spine Diseases, Glostrup Hospital, Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, University of Copenhagen, Denmark, Glostrup, Denmark, ²Department of Rheumatology, Slagelse University Hospital, Slagelse, Denmark, ³Department of Radiology, Sheba Medical Center, Tel Hashomer, Israel, ⁴Reumatologi, Kong Christian X's Gigthospital, Grasten, Denmark, ⁵DANBIO, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, ⁶Department of Radiology, Aarhus University Hospital, Aarhus, Denmark, ⁷University Hospital at Southern Denmark, Odense, Denmark, ⁸Department of Radiology, Copenhagen University Hospital Herlev, Copenhagen, Denmark, ⁹Department of Radiology, University Hospital at Southern Denmark, Odense, Denmark, ¹⁰Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark, ¹¹University of Southern Denmark, Odense, Denmark, ¹²ZiteLab ApS, Copenhagen, Denmark, ¹³Department of Rheumatology, University Hospital at Southern Denmark, Vejle, Denmark, ¹⁴Department of Rheumatology, Odense University Hospital, Odense, Denmark, ¹⁵Department of Rheumatology, Copenhagen University Hospital, Gentofte, Denmark, ¹⁶Center for Rheumatology and Spine Diseases, Glostrup Hopital, Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Rigshospitalet - Glostrup, University of Copenhagen, Denmark, Glostrup, Denmark

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: MRI and rheumatoid arthritis (RA)

Session Information

Date: Monday, November 9, 2015

Title: Imaging of Rheumatic Diseases Poster II: X-ray, MRI, PET and CT

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: MRI has proved to be more sensitive than clinical examination and x-ray for detection of inflammatory and destructive joint changes in early rheumatoid arthritis (RA) and to discriminate between treatment arms in clinical trials using the semi-quantitative Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA MRI scoring (RAMRIS) system. We aimed to investigate whether MRI-determined measures of disease activity and joint destruction were suppressed in early RA patients following a treat-to-target strategy with methotrexate (MTX) and intraarticular (i.a.) betamethasone and to investigate whether concomitant cyclosporine (CYA) had an additional effect on MRI determined inflammatory and destructive findings over 2 years.

Methods: In the 2-year randomized, double-blind, multicenter, clinical, treat-to-target trial, CIMESTRA, 160 patients with early (<6 months) RA were treated with MTX, i.a. betamethasone and CYA/placebo CYA of wich129 patients participated in the MRI substudy. Patients had contrast-enhanced MRIs at months 0, 6, 12 and 24 that covered the non-dominant wrist (wrist-only group) and if technically possible both wrist and metacarpophalangeal (MCP) joints (wrist+MCP group). MRIs were evaluated by an experienced radiologist blinded to patient identity, clinical and biochemical data but not to chronology, using the RAMRIS scoring system assessing inflammatory (osteitis, synovitis, tenosynovisits) and destructive (bone erosion, joint space narrowing) changes. Observed data, without any data imputations, are reported. Non-parametric statistics were used. A value of p<0.05 was considered statistically significant.

Results: MRI-results from the wrist-only group are shown in table 1. The data in the wrist+MCP group were overall similar (data not shown). No statistically significant differences between the treatment groups were observed in any MRI characteristics at baseline or at any follow-up time point. Both the wrist-only group and the wrist+MCP group showed significant reductions compared to baseline in osteitis, synovitis and tenosynovitis at 6 months (all parameters) and 12 and 24 months (synovitis and tenosynovitis). Statistically significant, but numerically low, increases in erosion and JSN scores from baseline to 6, 12 and 24 months were seen.

Conclusion: A treat-to-target strategy with MTX and i.a. betamethasone reduced MRI inflammatory findings significantly, with no additional effect of CYA, but still minor structural damage progression was observed.

Table 1

MRI status scores

– Wrist only group

Treatment group A

Methotrexate + placebo cyclosporine

n=58

Treatment group B

Methotrexate + cyclosporine

n=71

All

n=129

Baseline

6 Months

12 Months

24 Months

Baseline

6 Months

12 Months

24 Months

Baseline

6 Months

12 Months

24 Months

MRI measures

Osteitis

(0-24) n

129

119

126

118

Mean +/- SD

2.6±6.6

1.8±5.4

2.4±6.8

2.0±5.7

3.1 ±9.3

1.1±1.8

2.0±5.5

1.3±2.2

3.0 ± 8.2

1.4 ± 3.8

2.2 ± 6.1

1.6 ± 4.3

Median(range)

0 (0-33)

0 (0-27) ^NS

0 (0-37)^NS

0 (0-38) ^NS

0 (0-63)

0 (0-10)^NS

0 (0-34)^NS

0 (0-10)^NS

0 (0-63)

0 (0-27)*

0 (0-37)^NS

0 (0-38)^NS

Synovitis

(0-9) n

129

118

125

117

Mean +/- SD

4.8±3.1

2.9±2.8

3.3±2.9

2.5±2.8

4.4±3.1

3.1±2.7

2.7±2.3

2.2±2.4

4.6 ± 3.1

3.0 ± 2.7

3.0 ± 2.6

2.3 ± 2.6

Median(range)

5.5 (0-9)

2 (0-9)***

3 (0-9)***

1 (0-9)***

4 (0-9)

3 (0-9)***

2 (0-9)***

1 (0-9)***

5 (0-9)

3 (0-9)***

1 (0-9)***

Tenosynovitis

(0-30) n

129

118

125

117

Mean +/- SD

4.7±5.4

1.6±3.2

1.4±3.1

1.1±3.2

6.3±6.6

2.1±3.8

2.3±4.1

2.0±4.2

5.5 ± 6.1

2.1 ± 3.8

1.9 ± 3.7

1.6 ± 3.8

Median(range)

3 (0-27)

0 (0-15)***

0 (0-18)***

0 (0-20)***

5 (0-30)

0 (0-19)***

0 (0-17)***

0 (0-20)***

4 (0-30)

0 (0-19)***

0 (0-18)***

0 (0-20)***

Bone erosion

(0-150) n

129

119

126

118

Mean +/- SD

1.9±4.3

2.3±5.3

3.0±6.0

3.3±6.4

1.5±2.4

1.9±3.5

2.3±3.5

1.7 ± 3.4

2.1 ± 4.4

2.4 ± 4.8

2.8 ± 5.1

Median(range)

0 (0-30)

0 (0-35)*

1 (0-34)***

1 (0-38)***

0 (0-13)

0.5 (0-23)*

0.5 (0-23)***

1 (0-18)***

0 (0-30)

0(0-35)**

1 (0-34)***

1 (0-38)***

JSN

(0-68) n

129

119

126

118

Mean +/- SD

0.9±2.9

1±3.2

1.5±4.7

1.4±4.2

0.3±1.0

0.4±1.1

0.6 ± 2.1

0.6 ± 2.3

0.8 ± 3.3

0.9 ± 3.1

Median(range)

0 (0-19)

0 (0-20)^NS

0 (0-27)*

0 (0-28)***

0 (0-7)

0 (0-7)^NS

0 (0-27)*

0 (0-7)*

0 (0-19)

0 (0-20)*

0 (0-27)**

0 (0-28)***

Values for MRI status scores at baseline, 6, 12 and 24 months are presented as mean±SD and medians (range). ^NS, not significant; *p<0.05; **p≤0.005, *** p<0.0005 compared with baseline. Comparison between groups were carried out using Mann-Whitney U-test and comparisons between time points were carried out using Wilcoxon´s signed-rank test. JSN: Joint space narrowing.

Disclosure: S. Moller-Bisgaard, None; B. J. Ejbjerg, None; I. Eshed, None; K. Horslev-Petersen, None; M. Lund Hetland, None; A. G. Jurik, None; J. Vallø, None; H. Thomsen, None; T. Torfing, None; K. Stengaard-Pedersen, None; P. Junker, None; N. Steen Krogh, None; T. Lottenburger, None; T. Ellingsen, None; L. Smedegaard Andersen, None; I. Hansen, None; H. Skjødt, None; A. Svendsen, None; U. Tarp, None; J. Pødenphant, None; J. K. Pedersen, None; H. Lindegaard, None; M. Østergaard, None.

To cite this abstract in AMA style:

Moller-Bisgaard S, Ejbjerg BJ, Eshed I, Horslev-Petersen K, Lund Hetland M, Jurik AG, Vallø J, Thomsen H, Torfing T, Stengaard-Pedersen K, Junker P, Steen Krogh N, Lottenburger T, Ellingsen T, Smedegaard Andersen L, Hansen I, Skjødt H, Svendsen A, Tarp U, Pødenphant J, Pedersen JK, Lindegaard H, Østergaard M. Effect of a Non Biologic Treat-to-Target Strategy on MRI-Determined Inflammatory and Destructive Changes in Early Rheumatoid Arthritis – Results from a 2-Year Investigator-Initiated Double-Blind Randomized Controlled Clinical Trial [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/effect-of-a-non-biologic-treat-to-target-strategy-on-mri-determined-inflammatory-and-destructive-changes-in-early-rheumatoid-arthritis-results-from-a-2-year-investigator-initiated-double-blind-rando/. Accessed .

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