Background/Purpose Methotrexate (MTX) is the recommended first-line DMARD for rheumatoid arthritis (RA) in most countries, however response is not universal. Non-adherence may explain this to some degree. The aim of this analysis was to (1) describe patient self-reported adherence to MTX over the first 6 months of therapy and (2) identify factors associated with non-adherence.

Methods Patients were enrolled in the Rheumatoid Arthritis Medication Study (RAMS) a 1 year prospective study of MTX new-users for RA in the UK. At baseline, data was collected on demographic factors, alcohol and smoking history, disease activity (DAS28) and disease duration. In addition patients completed the Health Assessment Questionnaire (HAQ), visual analogue scales (VAS) for pain and fatigue, The Beliefs about Medicines Questionnaire (BMQ), Brief Illness Perceptions Questionnaire (B-IPQ), Hospital Anxiety and Depression Scale (HADS), the EQ-5D quality of life questionnaire and the Compliance Questionnaire–Rheumatology (CQ-R), a self-report adherence measure. To measure adherence during the first 6 months after MTX commencement patients completed a weekly MTX diary detailing any missed doses including reasons. Proportional adherence was determined using number of non-adherent weeks compared to total number of eligible weeks. Nonadherence was defined as ≥1 dose missed against medical advice. The associations between patient characteristics, measures of illness and medicine cognitions, and adherence were assessed applying adjusted (age, sex, disease duration and disease activity) univariate logistic regression analysis.

Results Analyses included the first 392 patients recruited to RAMS who completed the 6 month diary (median age 61 years, 70% female, mean DAS28 = 4.3 [sd 1.3]. In total, 20% (n=80) of patients reported 174 non-adherent weeks. Reasons for non-adherent weeks included (% weeks): no reason given (30%), adverse effects (28%), feeling unwell/ suspected infection (18%), forgetting (12%), taking a drug holiday (9%) or delayed prescription refill (3%). Overall mean proportional adherence was very high (98%). Of adherent patients, 19% missed at least one dose under medical advice. Factors associated in adjusted analyses with being ever non-adherent included higher baseline DAS28 score (OR 1.31 per unit DAS28 (95%CI:1.06, 1.61) and lower baseline CQ-R score (0.95 per unit CQ-R 95%CI:0.92, 0.99). BMQ concern and necessity scores, HADS depression score, illness perceptions and other patient characteristics were not associated with adherence.

Conclusion Over 20% of individuals were nonadherent although as many patients missed doses under medical advice. The effects of relatively low levels of non-usage of MTX, either due to non-adherence or to advised withdrawal, on disease outcomes is yet to be evaluated, however, these data suggest that levels of overall adherence to MTX over the first 6 months of therapy were very high.

Table 1: Baseline characteristics of cohort and association with nonadherence

Baseline variable	n	Adherent	n	Nonadherent	Adjusted odds ratio (95%CI)Ɨ	p
Age (years)	304	61.4 (51.5-70.1)	79	59.7 (48.6-69.0)	0.98 (0.96-1.00)	0.103
Gender-female	307	210 (68.4%)	79	60 (75.9%)	1.19 (0.65-2.18)	0.578
Currently drinks alcohol	292	213 (72.9%)	83	53 (63.9%)	0.63 (0.37-1.12)	0.116
Currently smokes	305	49 (16.1%)	80	19 (23.8%)	1.50 (0.791-2.85)	0.214
Disease duration (months)	304	9.6 (4.5-31.4)	80	12.9 (5.4-28.9)	1.00 (1.00-1.00)	0.712
1 current co morbidity	312	99(31.7%)	80	25 (31.3%)	1.01 (0.55-1.85)	0.981
≥1 current co morbidity	312	49 (15.7%)	80	17 (21.3%)	1.56(0.75-3.22)	0.233
DAS-28	279	4.3 (3.3-5.3)	74	4.6 (3.9-5.7)	1.31 (1.06-1.61)	0.011*
VAS-pain	302	49 (28-70)	79	49 (25-73)	0.99 (0.98-1.00)	0.109
VAS-fatigue	304	50 (23-71)	78	59 (26-77)	1.00 (0.99-1.01)	0.780
Disability (HAQ)	303	1.0 (0.5-1.6)	80	1.1 (0.4-1.8)	0.89 (0.58-1.37)	0.595
HQOL (EQ-5D)	291	0.74 (0.62-0.80)	78	0.71 ( 0.62-0.80	3.59 (0.20-64.0)	0.384
Depression (HAD)	300	8 (7-9)	78	8 (7-9)	1.12 (0.89-1.41)	0.339
Anxiety (HAD)	295	13 (12-15)	77	14 (12-15)	1.13 (0.95-1.34)	0.178
Necessary beliefs (BMQ)	288	19 (17-23)	76	20 (17.5-22)	0.99 (0.91-1.06)	0.740
Concerns (BMQ)	291	15 (12-17)	77	16 (14-18)	1.02 (0.95-1.10)	0.527
B-IPQ	280	46 (38-53)	71	47 (39-55)	1.00 (0.97-1.03)	0.907
CQ-R	142	75.4(66.7-84.2)	36	69.3 ( 63.2-76.3)	0.95 (0.92-0.99)	0.009**
All values n(%) or median(IQR) unless stated.
*p < 0.05              ** P < 0.01                          Ɨadjusted for age, gender, DAS28, disease duration

---

« Back to 2014 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/early-adherence-to-methotrexate-in-rheumatoid-arthritis-ra-is-high-a-prospective-longitudinal-study-of-new-users/