Background/Purpose: In a double-blind placebo-controlled 2-year investigator-initiated trial of patients with early rheumatoid arthritis (RA), we investigated if additional adalimumab (ADA) for 1 year on top of an aggressive treat-to-target strategy with methotrexate (MTX) and intraarticular (i.a.) corticosteroid reduced disease activity. Previously published results after 1 yearshowed that >75% of patients in both groups achieved low disease activity, but remission rates and physical function were higher in the ADA group¹. Here we present results from the 2nd year.

Methods: DMARD-naïve early RA patients (n=180) were randomized 1:1 to receive i.a. triamcinolone (40 mg/ml) in any swollen joint and MTX (20 mg/wk) for two years in combination with placebo-ADA (MTX+PLA) or MTX+ADA (40 mg eow) during the first year. Oral glucocorticoids were not allowed. ADA/PLA was withdrawn after 1 yr. During year 2, in both treatment arms, ADA (40 mg eow) was only (re)initiated in patients with recurrence of active disease (DAS28CRP>3.2). Clinical response was assessed by DAS28(CRP), clinical disease activity index (CDAI), simplified disease activity index (SDAI) and ACR/EULAR remission criteria. Physical function was assessed by HAQ (health assessment questionnaire).

Results: Baseline characteristics were similar in the two groups: MTX+PLA/MTX+ADA: DAS28(CRP) 5.6(3.8-7.3)/5.5(3.8-7.8), p=0.53. After 2 years the median MTX dose and cumulated dose of i.a. triamcinolone were similar in the two groups (Table), and biologics were (re)initiated in 15%/17% of patients. During the 2^ndyear, disease activity (DAS28CRP, CDAI and SDAI) and HAQ scores decreased and ACR/EULAR remission rates increased in the MTX+PLA group. After 2 years, remission rates in MTX+PLA/MTX+ADA groups were: DAS28CRP remission: 69%/66%; CDAI remission: 55%/57%; SDAI remission: 54%/50%; ACR/EULAR(28 joints):44%/45% with no significant differences between MTX+PLA/MTX+ADA in any clinical outcome measure (p=0.36-1.00).

Conclusion: An aggressive treat-to-target strategy of i.a. triamcinolone and methotrexate in early RA provided excellent disease control at 2 years’ follow-up independent of 1 year induction therapy with adalimumab.

¹Hørslev-Petersen K et al. Ann Rheum Dis Online First 7 mar 2013

 

Table 1. Doses, disease activity, and remission rates at one and two years
	Year 1			Year 2
Treatment	MTX+ 1st YR PLACEBO	MTX+ 1st YR ADA	P	MTX+ 1st YR PLACEBO	MTX+ 1st YR ADA	P
MTX dose mg/wk	20 (15-20)	20 (7.5-20)	0.17	20 (10-20)	20 (7.6-20)	0.33
I.a. triamcinolone (ml cumulated)	7 (2-18.8)	5.4 (1.8-17.4)	0.08	0 (0-7)	0 (0-7.7)	0.19
Triple DMARD	32 %	16 %	0.018	31 %	20 %	0.15
Biologics (open trial)	7 %	7 %	1.00	15 %	17 %	0.97
DAS28CRP	2.6 (1.7-4.7)	2.0 (1.7-5.2)	0.009	2.0 (1.7-4.5)	2.0 (1.7-4.4)	0.97
CDAI	3.9 (0-13.6)	1.9 (0-15.4)	0.01	1.9 (0.1-14.5)	2.2 (0-15.2)	0.75
SDAI	5.0 (0.8-20.2)	2.7 (0.7-30.4)	0.006	2.8 (0.7-19.0)	3.3 (0.7-17.7)	0.36
DAS28CRP<3.2	76%	80%	0.65	84%	83%	1.00
DAS28CRP<2.6	49%	74%	0.001	69%	66%	0.79
CDAI≤2.8	41 %	61 %	0.01	55 %	57 %	0.87
SDAI<3.3	36 %	57 %	0.007	54 %	50 %	0.66
ACR/EULAR Boolean (28)	30 %	48 %	0.017	44 %	45 %	1.00
ACR/EULAR Boolean (40)	29 %	49 %	0.014	44 %	42 %	0.91
HAQ	0.25 (0-1.44)	0.13 (0-1.5)	0.40	0.13 (0-1.63)	0.13 (0-1.5)	0.37
Values are medians (5%/95% percentiles) or percentage. We used Mann-Whitney or Pearson’s chi-square tests. Analysis was by ITT with last observation carried forward. Completer analysis and ITT without imputations gave similar results.

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