Background/Purpose:

Data suggests patients with early, ACPA negative, rheumatoid (RA) and undifferentiated arthritis (UA) are less likely to achieve remission with MTX at 4 months in comparison to ACPA positive patients [1]. In patients with probable RA, MTX only delayed progression to RA in ACPA positive patients [2]. The objective was to determine whether response to MTX differs according to ACPA status in an early inflammatory arthritis cohort.

Methods:

Patients with UA or RA (2010 ACR/EULAR criteria) initiated on MTX as first-line DMARD up to December 2011 were identified from the Inflammatory Arthritis disease CONtinuum (IACON) registry in Leeds. Outcome measures at 6 months were remission (DAS28-CRP<2.6) and EULAR response. Outcomes were analysed where complete response datasets were available using with last observations carried forward for patients who stopped MTX or escalated to combination DMARD therapy prior to 6 months. Logistic regression was used to compare the rate of DAS28 remission and EULAR good response at 6 months, adjusting for DAS28 at baseline.

Results:

Of 78 patients commencing MTX monotherapy, 51 of 53 ACPA positive and 14 of 25 ACPA negative patients fulfilled 2010 RA criteria. Radiographic erosions were present in 6/35 (24%) ACPA negative and 11/53 (21%) ACPA positive patients. Table 1 displays baseline characteristics according to 2010 RA criteria and ACPA status. Over 6 months methotrexate was continued as monotherapy in 49 patients:  alternative DMARD(s) were added (n=25), cessation (n=1), enrolment in clinical trial (n=1), death (n=1) and loss to follow-up (n=2). Patients escalating to combination DMARD therapy did so at a median time of 3 months on a median (IQR) weekly dose of MTX of 20 mg (20 to 25mg). This was similar to the weekly dose of MTX at 6 months in patients continuing monotherapy (median 20; IQR 15 to 25). Datasets were complete for analysis of response in 60 patients (Table 2). Rate of remission was higher in ACPA positive patients; odds ratio(OR) 8.9, 95% confidence interval (CI) 2.0 to 40. There was a trend towards a superior rate of EULAR good response in ACPA positive patients at 6 months (OR 2.1, 95% CI 0.6 to 7.7).

Table 1: Baseline Characteristics

	RA (2010 criteria)		UA
	ACPA+ n= 51	ACPA- n= 14	ACPA+ n= 2	ACPA- n= 11
Age, mean (SEM)	53(2)	60(4)	58(15)	44(5)
Female, n (%)	36(71)	8(57)	1(50)	9(82)
Shared epitope, n positive/n tested (%)	20/22(91)	4/6(67)	Not recorded	8/9(89)
RF positive, n (%)	44(86)	5(36)	1(50)	1(9)
Symptom duration, median (IQR), wks	33(17-77)	32(11-62)	6, 77	28(25-91)
Erosions, n (%)	11(22)	6(43)	0	0
Joint involvement (M=medium, L=large, S=small joints): 1 M/L 2-10 M/L 1-3 S 4-10 S >10 (at least 1 S)	. 0 0 11(22) 14(28) 26(51)	. 0 0 3(21) 1(7) 10(71)	. 1(50) 0 1(50) 0 0	. 0 0 3(27) 8(73) 0

Table 2: Response at 6 months

ACPA Status	Escalation to combination DMARD therapy, n (%)	Weekly MTX dose in mg (IQR)	Baseline DAS28, median (IQR)	6 month DAS28, median (IQR)	Reduction in DAS28, median (IQR)	DAS28 Remission Baseline, n(%)	DAS28 Remission 6 months, n(%)	EULAR Response, n (%)
								Good	Moderate	None
Positive (n=38)	13(34)	20 (20 to 25)	3.9 (2.9 to 5.3)	2.5 (2.0 to 3.7)	1.1 (0.4 to 2.1)	8(21)	20(53)	13(34)	12(32)	13(34)
Negative (n=22)	8(36)	20 (15 to 25)	3.5 (3.0 to 4.6)	3.5 (2.5 to 4.2)	0.0 (-0.5 to 1.3)	5(23)	5(23)	4(18)	4(18)	14(64)

Conclusion:

Rate of remission was higher in ACPA positive vs ACPA negative patients, and there was a trend towards superior rate of eular response. Escalation of therapy was comparable between the groups. This data suggests that seronegative patients may be less responsive to MTX and may require a different treatment regimen.

References:

1. Wevers-de Boer K et al. Ann Rheum Dis 2012. Epub March 8.

2. van Dongen H et al. Arthritis Rheum 2007;56(5):1424-32.

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