Background/Purpose Methotrexate (MTX) is used in monotherapy or in combination with other DMARDs in the treatment of patients (pts) with rheumatoid arthritis (RA). We evaluated the effects of low and high MTX doses in combination with initiation of ADA on patient-reported outcomes (PROs), in MTX-inadequate responders (MTX-IR) with moderate-to-severe RA.

Methods

MUSICA (NCT01185288) was a double-blind, randomized, controlled trial evaluating the efficacy of 2 different dosages of MTX, 7.5 or 20 mg/week (wk) in combination with ADA (40 mg every other wk) for 24 wks in MTX-IR RA pts. Pts entering the study had been receiving ≥15 mg/wk MTX for at least 12 wks. At each study visit, from baseline (BL) to wk 24, the following PROs were recorded: physical functioning, work productivity and activity impairment, and health-related quality-of-life (HRQoL), using the health assessment questionnaire-disability index (HAQ-DI), work productivity and impairment (WPAI), and the short-form 36 (SF-36) questionnaires, respectively. Last observation carried forward (LOCF) was used to account for missing values.

Results

154 pts were enrolled in the 7.5 mg/wk MTX+ADA arm, and 155 pts in the 20 mg/wk MTX+ADA arm. Both arms were similar for BL demographics (mean age 54.8, mean disease duration 5.3 years) and disease characteristics (mean DAS28(CRP) of 5.8). In the low and high MTX dosage groups respectively, mean BL HAQ-DI scores were 1.5, mean percentages (%) of time in absenteeism at BL were 9.2 and 10.1; mean % of time in presenteeism at BL were 45.0 and 47.6; mean % of activity impairment at BL were 57.0 and 61.9. BL SF-36 (physical component) scores were 31.5 for both groups, and BL SF-36 (mental component) scores were 44.7 and 41.9 for the low and high-dosage groups respectively. After 24 wks, significant improvements from BL were observed for both MTX dosage groups, in the WPAI (except for absenteeism), HAQ-DI and the physical and mental components of the SF-36 (table). Differences in physical function, QoL and work productivity observed between the low and high dosage MTX groups were not statistically significant.

Table 1. Effect of treatment with ADA + low or high dose MTX on patient outcomes at week 24
Outcome measure	n	Change  from BL to wk 24, mean (95% CI)	P-value  (BL and wk 24 mean scores)		wk 24, mean score (95% CI)	P-value (between wk 24 mean scores of dosage groups)
HAQ
7.5mg/wk MTX+ADA	151	-0.5 (-0.6, -0.4)	<.001		1.0 (0.9, 1.1)		0.476
20mg/wk MTX+ADA	154	-0.5 (-0.6, -0.4)	<.001		1.0 (0.8, 1.1)
WPAI-absenteeism
7.5mg/wk MTX+ADA	63	-2.9% (-8.4, 2.5)		0.288	6.3% (1.9, 10.6)		0.261
20mg/wk MTX+ADA	61	0.6% (-7.1, 8.2)		0.882	10.6% (4.7,16.6)
WPAI-presenteeism
7.5mg/wk MTX+ADA	66	-17.9% (-24.5, -11.3)		<.001	27.1% (20.9, 33.3)			0.700
20mg/wk MTX+ADA	63	-21.0% (-28.4, -13.6)		<.001	26.7% (20.0, 33.3)
WPAI- Overall Work impairment
7.5mg/wk MTX+ADA	63	-19.0% (-26.6, -11.4)		<.001	29.2% (22.9, 36.4)		0.580
20mg/wk MTX+ADA	61	-17.5% (-26.5, -8.4)		<.001	32.7% (24.7, 40.7)
WPAI-Activity impairment
7.5mg/wk MTX+ADA	137	-14.9% (-19.6, -10.2)		<.001	42.1% (37.0, 47.3)		0.278
20mg/wk MTX+ADA	143	-20.4% (-25.3, -15.4)		<.001	41.5% (36.5, 46.6)
SF-36-physical component
7.5mg/wk MTX+ADA	150	7.2 (5.7, 8.7)		<.001	38.8 (37.0, 40.5)		0.835
20mg/wk MTX+ADA	152	7.4 (6.1, 8.8)		<.001	38.9 (37.3, 40.6)
SF-36-mental component
7.5mg/wk MTX+ADA	150	3.7 (1.9, 5.6)		<.001	48.8 (47.0, 50.5)		0.759
20mg/wk MTX+ADA	152	4.8 (2.9, 6.7)		<.001	46.5 (44.7, 48.3)
P-values between dosage groups at wk 24 determined by ANCOVA

Conclusion

Similar to observations in pts with early RA,¹the addition of ADA to MTX in pts with moderate to severe disease and insufficient MTX response, led to improvements in physical function, work productivity and quality of life after 24 wks. The improvements were observed regardless of the MTX dosage. Similar improvements in the two MTX dosage groups support the idea that MTX dose could be reduced in some MTX-IR pts while initiating ADA therapy.

Reference:

1. Burmester GR et al. Ann Rheum Dis 2014;0:1-8

---

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/similar-improvements-in-physical-function-quality-of-life-and-work-productivity-among-rheumatoid-arthritis-patients-treated-with-2-different-doses-of-methotrexate-in-combination-with-adalimumab/