Table 2.

Overview of included studies: IBD

Authors and year	Sample characteristics, origin, and design	Factors measured				Analysis	Non-adherence: target, measure and extent
		Demographic	Clinical	Treatment	Psychosocial
Bermejo et al. (2010)	Sample: IBD outpatients N: 107 Mean age: 41.3 (SD = 11) Male: 40% Origin: Spain Design: cross-sectional Quality: 7/16 (43.8%)	Gender, marital status	Disease type, disease duration, disease activity, admissions/surgical procedures	Medication type, dosing frequency	Disease understanding	Univariate	Target	Oral and topical
							Measure	Self-report questionnaire
							Extent	69% (66% intentional/16% unintentional)
Bernal et al. (2006)	Sample: IBD outpatients N: 214 Mean age: 40.3 (SD = 13.5) Male: 13% Origin: Spain Design: cross-sectional Quality: 4/16 (25.0%)	Age, gender, employment status, educational level	Disease activity, disease duration, disease type, disease severity, disease related disability			Univariate	Target	Oral and topical
							Measure	Self-report questionnaire
							Extent	43.5% (unintentional) 8% (intentional)
Billioud et al. (2011)	Sample: CD outpatients N: 108 Median age: 35 (range 27–44) Male: 38% Origin: France Design: Cross-sectional Quality: 11/16 (68.8%)	Age, gender, marital status	Family history, disease type, disease duration, relapse history, age at diagnosis, previous investigations, past hospitalization	Concomitant treatment, medication dose	Lifestyle (smoking)	Univariate and multivariate	Target	Biologics (adalimumab)
							Measure	Self-reported questionnaire (reported missed or delayed injection)
							Extent	45.5%
Bokemeyer et al. (2007)	Sample: CD outpatients N: 49 Median age: 38 (range 17–68) Male: 49.2 Origin: Germany Design: cross-sectional Quality: 9/16 (56.3%)	Age, gender, employment status	Disease duration, disease activity, previous surgery	Medication dose, medication frequency, disease duration	Treatment concerns	Univariate	Target	Oral NSAIDs (AZA)/5 ASA
							Measure	Thiopurine S-methyltransferase (TPMT) and questionnaire (VAS)
							Extent	9.2% (TPMT)and 7.1% (VAS)
Carter et al. (2012)	Sample: CD population, medical and pharmacy claims data N: 448 Age: 42.6 (SD = 14.8) Male: 44% Origin: USA Design: retrospective observational cohort Quality: 9/16 (56.3%)	Age, gender, region	Outpatient visits, number of hospitalizations	Concomitant medication		Univariate	Target	Biologic (Infliximab)
							Measure	Medication possession ratio ≥80%
							Extent	23%
Červený et al. (2007)	Sample: IBD outpatients N: 177 Mean age: 36.9 (SD NR) Male: 47.5% Origin: Poland Design: cross-sectional Quality: 5/16 (31.3%)	Age, gender, marital status, educational level, employment status	Disease type	Medication type	Lifestyle (smoking),	Univariate	Target	IBD medications (all)
							Measure	Self-reported interview
							Extent	38.9%
Cerveny et al. (2007)	Sample: IBD outpatients N: 396 Mean age: 38 (SD NR) Male: 51% Origin: Czech Republic Design: cross-sectional Quality: 7/16 (43.8%)	Age, gender, marital status, educational level, employment status	Disease activity, disease type	Medication type	Lifestyle (smoking)	Univariate	Target	IBD medications (all)
							Measure	Self-reported questionnaire
							Extent	42.6% (involuntary non-adherence) 32.5% (voluntary non-adherence)
D’Inca et al. (2008)	Sample: IBD outpatients N: 267 Mean age: 41 (SD NR) Male: 51% Origin: Italy Design: cross-sectional Quality: 8/16 (50.0%)	Age, gender, marital status, educational level, employment status	Disease activity, disease duration, disease type, clinical status	Medication type, number of medications, dosing frequency, multiple daily doses	Forgetting, practical barriers (working day)	Univariate and multivariate	Target	Oral and rectal
							Measure	Self-reported questionnaire
							Extent	39%
Ediger et al. (2007)	Sample: IBD population N: 326 Mean age: 41 (SD = 14.06) Male: 40% Origin: Canada Design: cross-sectional Quality: 15/16 (93.8)	Age, gender, marital status, educational level, employment status	Disease type, disease activity, disease duration	Medication type, dosing frequency	Anxiety (HAQ), treatment concerns, treatment necessity, mastery, personality (agreeableness, openness, conscientiousness, extraversion, neuroticism), practical barriers	Multivariate	Target	IBD medication not specified
							Measure	Self-reported questionnaire (MARS)
							Extent	35% (27% men; 37% women)
Goodhand et al. (2013)	Sample: IBD outpatients N: 144 Mean age: adults-40 (SD = 1.5); young adults-20 (0.2) Male: adults-62%, young adults-51% Origin: UK Design: cross-sectional Quality: 8/16(50%)	Age, gender, ethnicity, marital status, employment status, education level, SES	Co-morbidity, disease duration, Disease type (CD, UC, IBDU), disease activity, age at diagnosis, hospital visits (OPC, hospital admissions)	Daily dose frequency, pill Burden (no of pills per day), medication type, concomitant medications	Anxiety, depression, Lifestyle (smoking, alcohol)	Univar ate and Multivariate	Target	Thiopurine
							Measure	Self-reported questionnaire (Morisky Medication Adherence Scale—MMAS-8) 6-TGN levels
							Extent	12%
Hovarth et al. (2012)	Sample: IBD outpatients N: 592 CD Median age: 38 (15–81) Male: 46% Origin: Hungary Design: cross-sectional Quality: 7/16 (44%)	Gender, educational level	Disease type, disease activity, functional disability, CAM use, previous surgeries	Medication type (immunomodulator use)	H-QoL, need for psychologist, Lifestyle (smoking)	Univariate	Target	Aminosalicylates, corticosteroids, immunomodulators, biological therapy
							Measure	Self-reported questionnaire
							Extent	13.4%
Horne et al. (2009)	Sample: Members of the National Association for Colitis and Crohn’s disease (NACC) N: 1871 Mean age: 50.1 (SD = 15.9) Male: 37% Origin: USA Design: cross-sectional Quality: 12/16 (75.5%)	Age, gender	Disease type, disease duration, GP visits, outpatient visits, inpatient visits		Treatment necessity, treatment concerns, attitudinal group	Multivariate	Target	IBD medications not specified
							Measure	Self-reported questionnaire (MARS)
							Extent	28% (unintentional) 32% (altered dose) 17% (stopped)
Kamperidis et al. (2012)	Sample: IBD outpatients N: 189 Mean age: 38 (SD = 1.0) Male: 55% Origin: USA Design: cross-sectional Quality: 8/14 (57.1%)	Age, gender, ethnicity, SES	Disease type, disease activity	Concomitant medication		Univariate and multivariate	Target	Biologics
							Measure	Thiopurine in urine
							Extent	8%
Kane et al. (2001)	Sample: IBD outpatients N: 94 Median age: 42.5 (range 18–79) Male: 51% Origin: USA Design: cross-sectional Quality: 6/14 (42.9%)	Age, gender, marital stat us, employment status, insurance type	Disease activity, recent endoscopy, family history, length of remission	Concomitant medication	QOL	Univariate and multivariate	Target	Oral NSAID (5-ASA)
							Measure	MED-TOTAL formula—refill and patient records
							Extent	60.0%
Kane (2006)	Sample: CD outpatient database N: 274 Age: NR Male: 42.3% Origin: USA Design: retrospective cohort Quality: 7/16 (43.8%)	Age, gender (female), ethnicity, marital status, education, insurance type, area code	Disease type, time since 1st infusion (>18 weeks)	Concomitant medication		Univariate and multivariate	Target	Infliximab (biologic)
							Measure	Clinic appoint no show
							Extent	15.0% (at least one no show)
Kane et al. (2009)	Sample: CD patients on national database N: 571 Mean age: 38.5 (15.0) Male: 45% Origin: USA Design: Longitudinal Quality: 9/16 (56.3%)	Age, gender	Co-morbidities, hospitalization, Outpatient visit, healthcare resource utilization and costs	Concomitant medications	NR	Univariate and multivariate	Target	Biologic (Infliximab)
							Measure	Prescription refills
							Extent	34.3%
Kane et al. (2011)	Sample: CD patients on national database N: 44,191 Mean age: NR Male: 37.3% Origin: USA Design: longitudinal Quality: 4/14 (28.6%)			Medication type	NR	Univariate	Target	Oral NSAID (5-ASA, balsalazide + olsalazine)
							Measure	Prescription refill rates
							Extent	87% (at 12 months)
Lachaine et al. (2013)	Sample: UC patients: Prescription claims database N: 12,756 Mean age: 55.3 (SD = 17.8) Male: 43% Origin: Canada Design: retrospective longitudinal Quality: 7/12 (58%)	Age, gender	Co-morbidities	Time of corticosteroids use (previous, current)		Multivariate	Target	5-ASA
							Measure	MPR (Medication Possession Ratio)
							Extent	80% + adherence at 12 months: 27.7% Persistence at 12 months: 45.5%
Lakatos (2009)	Sample: IBD outpatients N: 655 Mean age: 44.9 (SD = 15.3) Male: 46% Origin: Hungary Design: cross-sectional Quality: 9/116 (56.3%)	Educational level (CD only)	Disease duration, previous surgery (CD only), last follow-up visit (CD only)	Concomitant medications		Univariate and multivariate	Target	Oral and biologic
							Measure	Self-reported questionnaire
							Extent	CD: 20.9% UC: 20.6%
Linn et al. (2013)	Sample: IBD outpatients N: 68 Mean age: 40.5 (SD = 14.9) Male: 38% Origin: The Netherlands Design: prospective Quality: 11/16 (68.8%)	Age, education		Medication type	Recall of medical information	Multivariate	Target	Azathioprine, 6-mercaptopurine, Infliximab Methotrexate, 6-thioguanine, or Adalimumab
							Measure	Self-reported question
							Extent	Mean adherence (SD) = 9.1 (1.2) (range 1–10)
Mantzaris et al. (2007)	Sample: IBD outpatients N: 28 Mean age: 34.6 (SD = 9.2) Male: 46.6% Origin: Greece Design: prospective Quality: 8/16 (50.0%)	Age, gender, marital status	Family history, disease location, disease duration, prior surgery, disease activity	Concomitant medications	Lifestyle (smoking), QOL	Univariate	Target	Oral (azathioprine)
							Measure	Self-reported number daily pills
							Extent	74.3%
Mitra et al. (2012)	Sample: UC patients from insurance claims database N: 1693 Mean age: 42.3 (SD = 12.8) Male: 50.4% Origin: US Design: retrospective longitudinal Quality: 8/12 (66.7%)	Age, gender, geographic region, health plan type, insurance type	Healthcare costs, healthcare utilization, co-morbidity			Multivariate	Target	5-ASA
							Measure	MPR
							Extent	72%
Moradkhani et al. (2011)	Sample: convenience sample from IBD support group forum N: 111 Mean age: 31 (SD = 8.5) Male: 22.5% Origin: USA Design: cross-sectional Quality: 11/16 (68.8%)	Age, gender, ethnicity, SES, employment, education, marital status	Disease type, disease activity (pt rating and physician), disease duration, setting of IBD care		Disease understanding,	Univariate	Target	IBD medications not specified
							Measure	Self-reported questionnaire (Morisky)
							Extent	Mean score 1.68 (SD = 1.43)
Moshkovska et al. (2009)	Sample: IBD outpatients N: 169 Mean age: 49 (SD NR) Male: 51% Origin: UK Design: cross-sectional Quality: 9/16 (56.3%)	Age, gender, ethnicity, SES	Disease duration	Medication type, treatment center	Treatment necessity, treatment concerns, satisfaction with information about medicines (SIMS) [HCP–patient relationship]	Univariate and multivariate	Target	NSAID (5-ASA)
							Measure	Urine and self-reported questionnaire
							Extent	40% (urine), 34% (self-report)
Nahon et al. (2011)	Sample: IBD outpatients N: 1663 Mean age: 31 (SD = 8.5) Male: 22.5% Origin: USA Design: cross-sectional Quality: 7/16 (43.8%)	Age, gender, marital status, educational level, SES	Disease type, disease activity, disease duration, disease severity, surgery anoperineal location, family history	Medication type, complicated dosing regimen, number of tablets, lack of physician info, impact of schedule on daily life	Lifestyle (smoking), anxiety, mood, depression, feeling well, patient association member	Univariate and multivariate	Target	IBD medications not specified
							Measure	Self-reported questionnaire (visual analog scale)
							Extent	10.4%
Nahon et al. (2012)	Sample: IBD patients N: 1663 Mean age: 43.6 (SD = 15.4) Male: 26% Origin: France Design: cross-sectional Quality: 7/15 (46.7%)				Anxiety, depression	Univariate and multivariate	Target	Immunosuppressant, aTNF-a, 5-ASA, corticosteroids
							Measure	Self-reported (VAS)
							Extent	10%
Nguyen et al. (2009)	Sample: IBD outpatients N: 235 Mean age: 42.2 (SD = 14.2) Male: 43% Origin: USA Design: cross-sectional Quality: 10/16 (62.5%)	Age, gender, ethnicity, educational level, marital status, employment status, health insurance	Disease severity, disease type, attained age	Concomitant medication	HCP–patient relationship, QOL	Univariate, multivariate	Target	IBD medications not specified
							Measure	Self-reported questionnaire
							Extent	35.0%
Nigro et al. (2001)	Sample: IBD outpatients N: 85 Mean age: Not stated Male: 45% Origin: Italy Design: cross-sectional Quality: 9/16 (56.3%)	NR	Disease duration, disease severity		Psychiatric disorder [emotional well-being]	Univariate and multivariate	Target	IBD medications not specified
							Measure	Self-reported questionnaire
							Extent	7.0% non-compliant; 10.5% partial (details not provided)
Robinson et al. (2013)	Sample: IBD patients from drug records N: 568 Mean age: 56 (SD = NR) Male: 51% Origin: UK Design: retrospective cohort Quality: 8/12 (66.7%)		Relapse history	Medication type, treatment switches			Target	Mesalazine formulations
							Measure	MPR
							Extent	61%
San Román et al. (2005)	Sample: IBD outpatients N: 40 Mean age: 39.4 (SD = NR) Male: 50% Origin: Spain Design: cross-sectional Quality: 4/16 (25.0%)	Age, gender, education level, SES	Disease type disease duration, symptom duration, disease activity	Medication type, medication dose, treatment schedule	QOL, depression, HCP–patient relationship (discordance and trust), treatment understanding	Univariate	Target	Topical, oral, biologics (infliximab, adalimumab)
							Measure	Self-reported questionnaire
							Extent	72%
Selinger et al. (2013)	Sample: IBD outpatients N: 356 Mean age: Australia-47 (SD = NR), UK-46.8 (SD = NR) Male: Australia 45%, UK-38% Origin: Australia and UK Design: cross-sectional Quality: 11/16 (68.8%)	Gender, patient source (hospital clinic, office), marital status, employment, ethnicity, educational level, income	Disease type, disease duration, hospital admissions	Concomitant medication, medication type	Anxiety, depression, QoL, disease knowledge, necessity beliefs, treatment concerns, support group membership	Multivariate	Target	5-ASA, thiopurines, biological agent
							Measure	MARS
							Extent	28.7%
Selinger et al. (2014)	Sample: IBD patients from claims database N: 12,592 Mean age: 49 (SD = NR) Male: 42% Origin: US Design: longitudinal Quality: 7/12 (58.3%)	Age, gender		Medication type		Univariate	Target	5-ASA
							Measure	No prescription fill for at least 3 months
							Extent	Sulfasalazine 5-ASA: 22.3% (12 m), 11.9% (24 m) Non-sulfasalazine 5-ASA: 28.5% (12 m), 16.2% (24 m)
Sewitch et al. (2003)	Sample: IBD outpatients N: 153 Mean age: 37 (SD = 15.1) Male: 43% Origin: Canada Design: prospective Quality: 13/16 (81.3%)	Age, gender, educational level, income, marital status, language	Disease type, disease duration, new patient status, disease activity, physician duration, length of visit, further test recommendation, appointment rescheduling, consulting other HCP	Medication type	HCP–patient relationship, psychological distress, treatment efficacy, social support, [perceived stress, stressful events—emotional well-being], lifestyle (smoking)	Multivariate + sensitivity analysis	Target	IBD medications (all)
							Measure	Self-reported questionnaire
							Extent:	41.2%
Shale and Riley (2003)	Sample: IBD outpatients N: 98 Median age: 49 (range 17−85) Male: 51% Origin: UK Design: Cross-sectional Quality: 9/16 (56.3%)	Age, gender, marital status, educational level, employment status	Disease type, disease severity, disease duration, disease activity, relapse frequency	Medication dose, medication frequency, concomitant medications	Treatment efficacy, QOL, HCP–patient relationship, depression, anxiety, membership of patient group	Univariate and multivariate	Target	NSAIDs (Asacol:5-ASA)
							Measure	Self-reported questionnaire, urinary ASA
							Extent	Self-report 48%/urinary ASA 12%
Taft et al. (2009)	Sample: Self-reported IBD N: 211 Mean age: 46.5 (SD NR) Male: 23% Origin: USA Design: cross-sectional Quality: 11/16 (68.8%)	Age, gender, ethnicity, educational level, marital status	Disease duration, flare (frequency, duration and severity), remission of symptoms, previous surgery		Stigma	Univariate and multivariate	Target	IBD medications not specified
							Measure	Self-reported questionnaire (MTBS)
							Extent	Mean score (SD) CD: 0.98 (1.19), UC: 1.02 (1.22)
Waters et al. (2005)	Sample: IBD outpatients N: 89 Age: 45 (SD = 13.5) Male: 57% Origin: USA Design: RCT Quality: 9/16 (56.3%)	Age, gender (female), internet use (higher use), Crohn’s and Colitis Foundation Membership (not a member)		Frequency of physician visits		Univariate	Target	IBD meds (all)
							Measure	Patient diary
							Extent	54%
Yen et al. (2012)	Sample: IBD patients from claims database N: 5644 Mean age: 48.3 (SD = 15.4) Male: 47% Origin: Australia Design: longitudinal Quality: 8/12 (66.7%)	Age, gender, health plan type (persistence only), insurance type, geographical region (adherence only)	Never receiving specialist care, co-morbidities (persistence only)	Medication type, medication administration route (adherence only), previous treatment (adherence only), no switch from index drug (adherence)		Multivariate	Target	5-ASA medications
							Measure	Persistence: time to discontinuation Adherence: MPR
							Extent	Non-adherence: 79% Discontinuation of index drug (over 12 month period): 68.7%

Factors found to be associated with treatment adherence highlighted in bold

5-ASA 5-aminosalicylic acid, 6-TGN 6-thioguanine nucleotide, IBDU inflammatory bowel disease unclassified, ASA Acetylsalicylic acid, aTNF anti-tumor necrosis factor, AZA azathioprine, CAM complementary and alternative medicine, CD Crohn’s disease, GP general practitioner, HAQ health assessment questionnaire, HCP health care professional, H-QoL health-related quality of life, IBD inflammatory bowel disease, MARS medication adherence report scale, MMAS Morisky medication adherence scale, MPR medication possession ratio, MTBS medication taking behavior scale, NR not recorded, NSAID non-steroidal anti-inflammatory drug, OPC outpatient clinic, QOL quality of Life, SD standard deviation, SES socioeconomic status, SIMS satisfaction with information about medicines, TPMT thiopurine S-methyltransferase, UC Ulcerative colitis, VAS visual analog scale