Medication adherence in patients with rheumatoid arthritis: a critical appraisal of the existing literature

Figures & data

Figure 1. Simplified model to concordantly discuss a patient’s main barriers for medication adherence.

Intentional due to an imbalance between perceived benefits and concerns and unintentional due to practical barriers. During this discussion, the patient’s expertise and beliefs are fully valued.

Table 1. Search strategy in PubMed for retrieving studies on medication adherence in rheumatoid arthritis.

Boolean operator	Text words and Medical Index Subject Headings
	Arthritis, rheumatoid [mesh terms] or rheumatoid arthritis[tw]
AND	Medication adherence [mesh terms] or patient compliance [mesh terms]-or-(medication[tw] or medicine[tw] or medicines[tw] or medical[tw] or therapy[tw] or therapie[tw] or drug[tw] or drugs[tw]) and (complian* or non-complian* or non complian* or noncomplian* or adher* or non-adher* or non adher* or nonadher* or persist* or non-persist* or non persist* or nonpersist*)
AND	adult[mesh terms] or mature [tw] or adult [tw]

Table 2. Methods to assess adherence.

Method of assessment	Advantage	Disadvantage
Subjective
Self-report	Easy to use Readily available Noninvasive Sensitive for nonadherence Inexpensive	No evidence that the drug is actually ingested Not accurate Patient is aware of the measurement
Physicians’ estimation	Easy to use Inexpensive Noninvasive	Not accurate
Direct
Biomarkers (drug concentration/metabolites)	Objectively proves ingestion of the medication Accurate	Sensitive for white coat adherence Invasive Expensive Varies with individual difference in metabolism
Indirect
Pharmacy refill	Inexpensive Noninvasive Patient is not aware that they are being monitored	No evidence that the drug is actually ingested once filled
Tablet counts	Easy to use Inexpensive Noninvasive	No evidence that the drug is actually ingested once filled
Electronic monitors	Noninvasive Objective Provides additional information about dosing interval	Patient is aware of the measurement
Questionnaires	Easy to use Noninvasive Validation possible	Patient is aware of the measurement

Table 3. Studies assessing the extent of nonadherence to medication in rheumatoid arthritis.

Study (year)	Type of medication	Patients (n)	Study characteristics	Measure	Results (%)	Ref.
Studies measuring DMARD adherence
de Klerk et al. (2003)	Traditional DMARDs (SASA and MTX)	RA, polymyalgia and gout (127)	6 months longitudinal	MEMS	In the RA group: NSAIDs: 76–82 MTX :107 SASA: 72	[11]
Grijalva et al. (2010)	Traditional and biological DMARDs	RA (14,586)	Longitudinal	Refill data	Etanercept: 73 Leflunomide: 69 MTX: 59 Hydroxychloquine: 49 Sulfasalazine: 33	[12]
Borah et al. (2009)	Etanercept or adalimumab	RA (3829)	12 months longitudinal	Refill data	Adalimumab: 63 (naive users), 70 (existing users) Etanercept: 65 (naive users), 73 (existing users)	[13]
Curkendall et al. (2008)	Etanercept or adalimumab	RA (2285)	12 months longitudinal	Refill data	22–56 (depending on copayment)	[14]
Contreras-Yáñez et al. (2010)	DMARDs	RA (93)	6 months longitudinal	Interview	51	[6]
van den Bemt et al. (2009)	DMARDs	RA (228)	Cross-sectional	Interview Questionnaires (CQR/MARS)	99 66–67	[15]
Doyle et al. (1993)	DMARDs (penicillamine)	RA (59)	Cross-sectional	Chemical marker	39	[16]
Pullar et al. (1988)	DMARDs (penicillamine)	RA (26)	Cross-sectional	Patient interview Pill count Chemical marker Estimation physician	96 77 58 42	[17]
Brus et al. (1999)	DMARDs (sulfasalazine)	RA (55)	6 months randomized clinical trial	Pill count	82–91 (no difference between intervention and control)	[18]
Studies measuring both NSAID & DMARD adherence
Viller et al. (1999)	NSAIDs, DMARDs or corticosteroids	RA (592)	36 months longitudinal	Patient interview	Baseline adherence: 59–65 Consistent adherent: 35.7 Consistent nonadherent: 23.8	[7]
Tuncay et al. (2007)	NSAIDs, DMARDs or corticosteroids	RA (100)	12 months longitudinal	Interview	Baseline adherence: 52.3 Consistent adherent: 30.2 Consistent nonadherent: 11.6	[19]
Owen et al. (1985)	NSAIDs and DMARDs	RA (178)	Cross-sectional	Patient interview	63.5	[20]
Deyo et al. (1981)	NSAIDs or DMARDs	RA, OA, gout and AS (171)	6 months longitudinal	Refill rates	NSAID: 58–73 Penicillamine: 84 (n = 9)	[21]
Garcia-Gonzalez et al. (2008)	Not described	RA (70)	Cross-sectional	Interview	50	[22]
Park et al. (1999)	Not described	RA (121)	1 month longitudinal	MEMS	Perfect adherence in 38% of the patients	[53]
Taal et al. (1993)	Not described	RA (96)	Cross-sectional	Patient interview	93	[79]

AS: Ankolysing spondylitis; CQR: Compliance Questionnaire on Rheumatology; DMARD: Disease-modifying antirheumatic drug; MARS: Medication Adherence Report Scale; MEMS: Medication Event Monitoring System; MTX: Methotrexate; OA: Osteoarthritis; RA: Rheumatoid arthritis; SASA: Sulfasalazine.

Table 4. Factors associated and not associated with nonadherance in studies targeting disease-modifying antirheumatic drug adherence.

Study (year)	Type of medication	Patients (n)	Study characteristics	Factors associated with adherence	Factors not associated with adherence	Ref.
de Klerk et al. (2003)	Traditional DMARDs (sulfasalzine and methotrexate)	RA, polymyalgia and gout (127) Assessed with MEMS	6 months longitudinal	Condition-related factors: perceived health; and subcategories of overall health Patient-related factors: self-efficacy	Condition-related factors: functioning; and quality of life Patient-related factors: coping Therapy-related factors: side effects	[11]
Borah et al. (2009)	Etanercept or adalimumab	RA (3829) Assessed with refill data	12 months longitudinal	Therapy-related factors: naive vs existing users		[13]
Curkendall et al. (2008)	Etanercept or adalimumab	RA (2285) Assessed with refill data	12 months longitudinal	Socioeconomic factors: gender; and residence Healthcare system: HMO insurance; and out-of-pocket payments Therapy-related factors: prior DMARDs		[14]
Contreras-Yáñez et al. (2010)	DMARDs	RA (93) Assessed with interview	6 months longitudinal	Condition-related factors: disease activity; and erythrocyte sedimentation rate	Socioeconomic factors: gender; age; education; socioeconomic status; and marital status Condition-related factors: functioning; comorbidity; and drug load	[6]
van den Bemt et al. (2009)	DMARDs	RA (228) Assessed with interview and questionnaires	Cross-sectional	Therapy-related factors: number of side effects Condition-related factors: disease activity Patient-related factors: BMQ necessity	Socioeconomic factors: age; gender; marital status; education; and tobacco use Condition-related factors: functioning; and number of medication Patient-related factors: BMQ concerns; and satisfaction with information	[15]
Brus et al. (1999)	DMARDs (sulfasalazine)	RA (55) Assessed with pill count	Randomized clinical trial (education vs standard care) 6 months follow-up	Patient-related factors: self-efficacy	Socioeconomic factors: education; age; and gender Patient-related factors: outcome expectation; and perceived social attitude/support Condition-related factors: pain; functioning; disease activity; and perceived barriers	[18]
Hill et al. (2001)	Penicillamine	RA (100) Assessed with pharmacological marker	Randomized clinical trial 12 weeks	Socioeconomic factors: education		[74]
Treharne et al. (2004)	NSAIDs, DMARDs or corticosteroids	RA (85) Assessed with questionnaires	Cross-sectional	Socioeconomic factors: presence of children Therapy-related factors: steroid use; and drug load Healthcare system: satisfaction consultation Patient-related factors: BMQ necessity; and beliefs about harms and overuse medication	Socioeconomic factors: gender; age; socioeconomic status; marital status; employment; living alone; and number of children Condition-related factors: disease duration; comorbidity; class of medication; and disease activity Patient-related factors: satisfaction social support; extent support; and optimism	[52]
Lorish et al. (1989 )	Not described	RA (200)	Cross-sectional	Socioeconomic factors: live alone; divorced; employed; years of education; financial status; and expense Therapy-related factors: side effects; and scheduled routines	Socioeconomic factors: family against taking medication Therapy-related factors: ran out of medication; interruption before taking; unclear dosing direction; price of the drugs; and medication stopped working Condition-related factors: physical functioning; improvement of the disease Patient-related factors: stress/hurry; forgetfulness; worries about long-term resistance	[57]
Viller et al. (1999)	NSAIDs, DMARDs or corticosteroids	RA (592)	36 months longitudinal	Socioeconomic factors: age; and gender Healthcare system: satisfactory contacts with healthcare provider Patient-related factors: knowledge about disease and treatment Condition-related factors: decreased disability	Socioeconomic factors: education	[7]
Tuncay et al. (2007)	NSAIDs, DMARDs or corticosteroids	RA (100)	12 months longitudinal	Socioeconomic factors: age	Socioeconomic factors: gender Condition-related factors: disease duration; number of medications; HAQ; disease activity; morning stiffness; erythrocyte sedimentation rate; CRP; and decreased disability Healthcare system: regularity insurance	[19]
Owen et al. (1985)	NSAIDs and DMARDs	RA (178) Adherence measured by patient interview	Cross sectional	Condition-related factors: erythrocyte sedimentation rate; and duration morning stiffness Patient-related factors: cited reason for taking drugs; and attitude to medication	Socioeconomic factors: gender; education; socioeconomic status; and residential location Condition-related factors: disability score; number of medications Therapy-related factors: type of medication; current/previous side effects; and number of daily doses Patient-related factors: perceived effectiveness of the medication; and level of pain	[20]
Garcia-Gonzalez et al. (2008)	Not described	RA (70)	Cross-sectional	Socioeconomic factors: education; and ethnicity Therapy-related factors: severity of side effects	Condition-related factors: disease duration; health status; and activity	[22]
Park et al. (1999)	Not described	RA (121)	1 month longitudinal	Socioeconomic factors: age Patient-related factors: busy lifestyle; cognitive deficits; and coping with arthritis-related moods	Condition-related factors: illness severity; medication load; and physical function	[53]

BMQ: Beliefs about Medication Questionnaire; CRP: C-reactive protein; DMARD: Disease-modifying antirheumatic drug; HAQ: Health Assessment Questionnaire; HMO: Health Maintenance Organization; MEMS: Medication Event Monitoring System; RA: Rheumatoid arthritis.

Activity Evaluation: Where 1 is strongly disagree and 5 is strongly agree

	1	2	3	4	5
1. The activity supported the learning objectives.
2. The material was organized clearly for learning to occur.
3. The content learned from this activity will impact my practice.
4. The activity was presented objectively and free of commercial bias.

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