Background/Purpose: The aim was to investigate if a treat-to-target strategy with methotrexate and intra-articular glucocorticoid suppressed synovitis and osteitis, and halted structural damage progression in early rheumatoid arthritis (ERA), and if added adalimumab provided an additional effect, as judged by magnetic resonance imaging (MRI).
Methods: In a double-blinded placebo-controlled investigator-initiated trial, 180 DMARD naïve ERA patients were randomized 1:1 to methotrexate, intra-articular glucocorticoid injections and placebo/adalimumab (1). Eighty-five patients (placebo/adalimumab: 43/42) had contrast-enhanced MRI of the right wrist and the 2nd-5thmetacarpohalangeal joints at months 0, 6 and 12. Synovitis, osteitis, tenosynovitis, bone erosion and joint space narrowing (JSN) were scored with validated methods (2–4).
Results: Synovitis, osteitis and tenosynovitis scores decreased highly significantly (p<0.0001) during the 12-months follow-up, with change scores of mean -3.7 (median -3.0[range -13;11]), -2.2 (-1 [-31;32]) and -3.3 (-1[-31;32]), respectively. No overall change in MRI erosion and JSN scores were observed, with change scores of 0.1 (0 [-16;13]) and 0.2 (0 [-3;4]), respectively. See table for status scores. Clinical disease activity scores and patient-related measures decreased highly significantly during follow-up (table). Among MRI, clinical and biochemical outcome measures, the tenosynovitis score at month 6 was the only measure that differed significantly between the treatment groups; placebo group: 3.9 (2 [0;18])/the adalimumab group: 1.3 (0 [0;11]), Mann-Whitney: p<0.035. Furthermore, the osteitis score decreased significantly from month 0 to month 6 and 12 in the adalimumab group, but not in the placebo group, Wilcoxon; p≤0.002 and p≥0.062, respectively.
|
Table. MRI and clinical status values for patients in the placebo and the Adalimumab treatment groups at 0, 6 and 12 months, mean (median [range]) |
|||
|
|
0 months |
6 months |
12 months |
|
Synovitis (0–21) Adalimumab group |
8.2 (8 [0–19]) 7.6 (7 [0–21]) |
4.9 (4 [0–13])*** 5.0 (5 [0–13])** |
4.7 (4 [0–15])*** 4.8 (4 [0–15])* |
|
BME (0–69) Adalimumab group |
6.2 (1 [3–35]) 4.3 (1 [0–34]) |
3.9 (0 [0–35])NS 1.4 (0 [0–11])** |
3.5 (0 [0–36])NS 2.1 (0 [0–31])* |
|
Tenosynovitis (0–30) Adalimumab group |
7.3 (5 [0–26]) 5.2 (3 [0–23]) |
3.9 (2 [0–18])* 1.3 (0 [0–11])*** |
2.0 (0 [0–20])** 1.6 (0 [0–30]))* |
|
Erosions (0–30) Adalimumab group |
12.5 (6 [0–64]) 10.9 (8 [0–43]) |
11.6 (5 [0–49])NS 9.9 (8 [0–30])NS |
13.7 (6 [0–61])NS 10.3 (8 [0–30])NS |
|
JSN (0–84) Adalimumab group |
1.1 (0 [0–8]) 0.6 (0 [0–7]) |
1.1 (0 [0–9])NS 0.6 (0 [0–7])NS |
1.4 (0 [0–12])NS 0.9 (0 [0–7])NS |
|
DAS28 Adalimumab group |
5.3 (5.2 [3.5–8.1]) 5.4 (5.4 [3.3–7.5]) |
2.7 (2.5 [1.7–5.0])*** 2.6 (2.4 [1.7–6.0])*** |
2.6 (2.3 [1.7–4.6])*** 2.4 (2.0 [1.7–4.7])*** |
|
Values are presented as mean (median [range]). The numbers in bold writing indicate differences between treatment groups. Between baseline and follow-up visit differences were tested using Mann-Whitney’s test: .NS: Not significant; *≤0.005; **≤0.001; ***<0.0001. |
|||
Conclusion:
A treat-to-target strategy with methotrexate and intra-articular glucocorticoid in ERA patients effectively decreased synovitis, osteitis and tenosynovitis and halted structural damage progression judged by MRI. The addition of Adalimumab provided further suppression of osteitis and tenosynovitis.
References: 1. Hørslev-Petersen K et al. Ann Rheum Dis. Online First 7 mar 2013; 2. Østergaard et al. J Rheumatol. 2003;30:1385-6; 3. Haavardsholm et al. Ann Rheum Dis. 2007;66:1216-20; 4. Østergaard et al. J Rheumatol. 2011;38:2045-50
Disclosure:
M. B. Axelsen,
Abbott Laboratories,
2;
I. Eshed,
None;
K. Hørslev-Petersen,
Abbott Laboratories,
2,
UCB Nordic,
5;
K. Steengaard-Petersen,
Abbott Laboratories,
5,
Wyeth Pharmaceuticals,
5,
Pfizer Inc,
5,
Danish Rheumatism Association,
2;
M. L. Hetland,
None;
J. M. Møller,
None;
P. Junker,
The Danish Rheumatism Association,
2;
J. Pødenphant,
None;
T. Ellingsen,
None;
P. Ahlquist,
None;
H. M. Lindegaard,
Lilly, MSD, Nordpharma, Roche Pharmaceuticals,
5;
A. Linauskas,
None;
A. Schlemmer,
: MerckSharpDohme,
5,
Roche Pharmaceuticals,
5,
Wyeth/Pizer,
5;
M. Yde Dam,
None;
I. Hansen,
None;
H. C. Horn,
Abbott Laboratories,
5;
C. G. Ammitzbøll,
None;
A. Jørgensen,
None;
S. B. Krintel,
None;
J. Raun,
None;
J. S. Johansen,
None;
N. S. Krogh,
None;
M. Østergaard,
Abbott, Pfizer, Centocor,
2,
Abbott Pfizer, Merck, Roche, UCB,
5,
Abbott, Pfizer, Merck, BMS, UCB, Mundipharma,
8.
ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-treat-to-target-strategy-with-methotrexate-and-intra-articular-triamcinolone-with-or-without-added-adalimumab-reduces-synovitis-osteitis-and-tenosynovitis-and-halts-structural-damage-progression-in/