. 2018 Jul 3;12:1151–1166. doi: 10.2147/PPA.S165101

Table 1.

Adherence and persistence

Study	Population and rheumatic disease	Study size	Type of medication	Adherence/persistence definition and measurement	Study outcome	Adherence/persistence (%)
Morgan et al³⁸ UK Prospective cohort Follow-up at baseline, 6, 12, and 18 months	First-time ADA users RA	329	ADA ADA+csDMARDs	Self-reported questionnaire CQR19 (mail) CQR score (0–100) CQR <65 low-adherence The extent to which a patient’s behavior in taking their medication corresponds to agreed recommendations by their health care provider	Adherence 6 months 12 months 18 months	76.76 76.32 76.7
Kumar et al²⁷ UK Cross-sectional	Existing users RA	180	csDMARDs or anti-TNFα	Self-reported questionnaire (interview) MARS-6 score (6–30) MARS $26 (high adherence) No definition cited in the article	Adherence White British South Asian	76.9 58.4
Gadallah et al²⁸ Egypt Cross-sectional	Existing users RA	140	csDMARDs+NSAIDs	Self-reported questionnaire Interview 1. MMAS-8 score (<6 low, 6–7 medium, and >8 high adherence) 2. Rate of prescription refilling Late/on time The extent to which patients take medications as prescribed by their health care providers 3. DAS28 score: DAS28>5.1 high disease activity. DAS28,3.2 low disease activity. DAS28<2.6 remission.	Adherence Low Medium High Rate of prescription refilling Late On time	90.7 9.3 0 75.7 24.3
Salaffi et al³⁰ Italy Observational 16 consecutive weeks Longitudinal 12-month follow-up	First-time users of bDMARDs RA	209	Subcutaneous anti-TNFα (ADA, ETN, GOL, or CET) ± MTX	Self-reported questionnaire (via post or email) A combination of compliance and persistence. MMAS-4 score 0 points = high adherence 1–2 points = average adherence 3–4 points = poor adherence	Adherence	79.4
Chu et al²⁴ USA Retrospective 1 and 2 years follow-up Claim database	First-time users of ADA or ETN RA	2,151	ADA or ETN ± csDMARDs, NSAIDs or analgesics	Adherence was measured with PDC (%) and treatment abandonment with attrition rate (%) $PDC (%) = \frac{Total days drug available}{Days of follow-up} \times 100$ PDC $80% adherent PDC, 80% nonadherent $Attrition = \frac{No . of patients abandoning medication}{No . of patiients initiating medication} \times 100$ Rate (%)	Adherence Treatment abandonment ADA ETN	26.8 42.9 32.2
Abdul-Sattar et al³² Egypt Cross-sectional	Existing users SLE	80	csDMARDs	CQR19 score (0–100) Nonadherent (noncompliant) = patients who were taking, 80% of their medication correctly	Adherence	52.5
Glintborg et al³⁶ Denmark Observational DANBIO registry	First-time users of anti-TNFα AS	1,576	Anti-TNFα (ADA, ETN, GOL, INF) ± MTX	Number of years each patient maintained treatment Start date = the date of the first given dose Stop date = the date of the first missed dose	Treatment duration mean (years) Current smokers Previous smokers Never smokers	2.24 2.71 4.12
Højgaard et al³⁷ Denmark Observational DANBIO registry	First-time users of anti-TNFα PsA	1,388	Anti-TNFα (ADA, ETN, or INF) ± MTX	Number of years each patient maintained treatment Start date = the date of the first given dose Stop date = the date of the first missed dose	Treatment duration mean (years) Current smokers Never smokers	1.56 2.43
Bonafede et al²⁵ USA Retrospective database 1-year follow-up	First-time users of dual or triple therapy RA	4,542	ETN–MTX vs MTX-HCQ-SSZ	Rate of adherence PDC* (%) = the percentage of days based on day’s supply of prescription claims during which a patient has medication available during the 1-year post-index period Adherent patient PDC*. 80% for all drugs within each regimen Rate of persistence (%) = no treatment gap. 45 days for any drug and no addition or switching to other csDMARDs	Adherence ETN–MTX MTX–HCQ–SSZ Persistence ETN–MTX MTX–HCQ–SSZ	27.9 18.2 29.4 23.2
Hromadkova et al³¹ Czech Republic Cross-sectional	RA AS SSc JIA	289	Not mentioned	Self-reported questionnaire CQR19 score CQR19 score $80% compliant CQR19 score, 80% non-compliant	Adherence RA AS	55.1 38.3
Betegnie et al³³ France Prospective cohort	Existing users AS RA PsA	581	bDMARDs ± csDMARDs	Questionnaire developed and validated by the authors (via the Internet) SD = patient’s decision to stop biologics	Adherence	85.2
De Cuyper et al²⁹ Belgium Observational 16 consecutive weeks	Existing users RA	129	MTX (oral or injection)	1. MEMS^® Medication adherence rate = Every patient was assigned a score 0 (not opened) or 1 (opened). The average of 16 measurements was multiplied by 100 Patient fully adherent = if, over a period of 1 week, the MEMS container was opened once or more in accordance with the prescription 2. MARS-5 (score range 5–25) 3. CQR19 score 4. VAS (ranging from “in 0% of the cases” to “in 100% of the cases”)	Adherence 1. MEMS 2. MARS-5 3. CQR19 4. VAS	92 Mean score 24.2 85.7 Mean score 94
Lyu et al³⁴ Germany Retrospective database 12 months follow-up	First-time users of subcutaneous anti-TNF therapy RA AS PsA	881	Anti-TNFα (ADA, ANA, CET, ETN, or GOL) ± csDMARDs	Rate of persistence assessed as time from initiation of treatment until discontinuation Discontinuation was the first day of a period of at least 60 consecutive days (grace period) in which no prescription for the biologic agent was detected (switching to another biologic agent was considered non-persistence)	Persistence RA AS PsA	51.9 48.1 57.9
Kim et al²⁶ USA Retrospective claim database	First-time users RA	2,685	csDMARDs (MTX, HCQ, SSZ, or LEF) as mono- or dual therapy	Adherence was measured with PDC PDC = the number of days when drugs were available divided by the number of days in the study period PDC $70% adherence PDC, 70% nonadherence Persistence was calculated as the number of days in which sDMARD were continuously used during the post-index period before a gap of the last day’s supply plus 60 days	Adherence Persistence (days)	10 189
Machado et al³⁵ Brazil Retrospective cohort Database 1 and 2 years follow up	First-time users RA AS	12,893	Anti-TNFα (ADA, ETN, or INF) ± csDMARDs (MTX, LEF, SSZ, HCQ, or CCQ) users and csDMARDs users	Proportion of persistent patients: $At the 1 - year follow-up = \frac{No . of patients who persisted in their therapies for at least 1 year}{No . of patients who had 2 years follow-up or more}$ $At the 2 - year follow-up = \frac{No . of patients who persisted in their therapies for at least 1 year}{No . of patients who had 2 years follow-up or more}$ In the anti-TNF group, switching from an anti-TNF drug to another was considered discontinuation of therapy Persistence = the period between the start of treatment until it is discontinued, allowing for an interval of up to 30 days between the prescription end and the start of the next prescription	Persistence Anti-TNFα ± sDMARD 1 year RA AS 2 years RA AS csDMARDs 1 year RA AS 2 years RA AS	66 80 41 60 54 41 29 20

Abbreviations: ADA, adalimumab; ANA, anakinra; AS, ankylosing spondylitis; CCQ, chloroquine; CET, certolizumab; CQR19, 19-item Compliance Questionnaire for Rheumatology; bDMARDs, biological disease-modifying antirheumatic drugs; csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; ETN, etanercept; GOL, golimumab; HCQ, hydroxychloroquine; INF, infliximab; JIA, juvenile idiopathic arthritis; LEF, leflunomide; MARS, Medication Adherence Report Scale; MMAS-8, 8-item Morisky’s Medication Adherence Scale; MEMS, Medication Event Monitoring System; MTX, methotrexate; NSAIDs, nonsteroidal anti-inflammatory drugs; RA, rheumatoid arthritis; PDC, proportion of days covered; PDC*, percentage of days covered; PsA, psoriatic arthritis; SD, self-discontinuation; SLE, systemic lupus erythematosus; SSZ, sulfasalazine; SSc, systemic sclerosis; VAS, Visual Analog Scale.