Medication adherence and persistence in patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis: a systematic literature review

Figures & data

Figure 1 PRISMA flowchart of included studies.

Table 1 Medication adherence study characteristics and results

Study	Type of study	Source of patient sample	Patient population	Length of follow-up (time period)	Adherence definitiona	Adherence rates (%)
RA studies
Chu et al^Citation21	Retrospective cohort	KPSC-EMRs	RA patients (N=2,151): ADA (n=564), ETN (n=1,587)	2 years (2002–2009)	PDC ≥80%	ADA (63), ETN (67)
Erhardt et al^Citation22	Retrospective cohort	VA clinical and administrative data	RA patients (N=2,296), veterans transitioning from MTX monotherapy: MTX + TNFi (n=2,125), MTX + HCQ + SSZ (n=171)	1 year (2006–2012)	PDC ≥80%	MTX + TNFi (26), MTX + HCQ + SSZ (11)
Oladapo et al^Citation23	Retrospective cohort	Texas Medicaid	RA patients (N=822; new biologic users) within 6 months of injection period: ETN (n=274), ADA (n=274), IFX (n=274)	1 year (2003–2011)	MPR ≥80%	ETN (16), ADA (21), IFX (38)
Tkacz et al^Citation24	Retrospective cohort	Optum Insight Clinformatics	RA patients (N=3,892) with previous prescriptions of biologics: ADA (n=1,532), ETN (n=2,099), GOL (n=261)	1 year (2009–2011)	MPR ≥80% and PDC ≥80%	ADA: MPR (71), PDC (70); ETN: MPR (62), PDC (61); GOL: MPR (82), PDC (81)
Li et al^Citation25	Retrospective cohort	MAX files	RA patients (N=2,638; new users of biologics): ETN (n=1,359), ANA (n=267), IFX (n=1,012)	1 year (2000–2002)	PDC ≥80%	ETN (32), ANA (11), IFX (43)
Borah et al^Citation26	Retrospective cohort	Managed care administrative claims data	RA patients (N=3,829), including new/experienced biologic users: ETN (n=2,537), ADA (n=1,292)	1 year (2005–2006)	MPR ≥80%	ETN: new users (65), experienced users (73); ADA: new users (63), experienced users (70)
Grijalva et al^Citation27	Retrospective cohort	Tennessee Medicaid managed-care program	RA patients (N=14,586) with previous therapeutic treatment (MTX, ETN, IFX, ADA)	NR (1995–2005)	Median MPR: The percent of person- time exposed to initial regimen during the episodes, as calculated for patients with 180+ person-days of follow-up	Median adherence: MTX (59), ADA (72), ETN (73), IFX (68)
Harley et al^Citation28	Retrospective cohort	Large US health plan	RA patients (N=2,662) receiving new biologic or new MTX treatment 182 days prior to study index: MTX (n=1,668), biologics (IFX [n =141], ETN [n=853])	1 year (NR)	Compliance ratio ≥80%: number of therapy administrations or filled prescriptions divided by the expected number	IFX (81), ETN (68), MTX (64)
Curkendall et al^Citation29	Retrospective cohort	MEDSTAT MarketScan Commercial Insurance claims	Newly initiated RA patients (N=2,285; ADA, ETN)	1 year (2002–2004)	Average MPR	Mean adherence (52)
Grijalva et al^Citation30	Retrospective cohort	Tennessee Medicaid managed-care program	RA patients (N=6,018) with previously filled regimen and a year of continuous health plan enrollment: DMARDs (MTX, HCQ, SSZ, LF) and biologics and MTX (IFX, ETN, ADA, ANA)	1 year (1995–2004)	Average MPR	Mean adherence for MTX (80), IFX (90), MTX + IFX (66), ETN (83), MTX + ETN (64), ADA (85), MTX + ADA (72)
Barlow et al^Citation31	Retrospective cohort	Prescription benefit plans of Medco Health Solutions, Inc.	RA patients (N=4,388) with one previous prescription of assigned biologic and continuous drug/medical benefit (ETN, ADA): Group 1 – specialty pharmacy (n=3,054); Group2 – retail pharmacy (n=1,334)	1 year (2006–2008)	Average MPR: Defined as the proportion of days covered by medication supply during the 1-year fixed interval	Mean adherence for Group 1, years 1–3: (63, 68, 61); Group 2, years 1–3 (50, 51, 44)
Ellis et al^Citation32	Retrospective cohort	Truven database	RA patients (N=1,036) with first or most recent prescription for GOL	NR (2008–2010)	The number of refills occurring between 21 and 38 days from a previous fill divided by the total refill intervals	GOL (79)
Stockl et al^Citation33	Prospective cohort	PBM DTM program	RA patients (N=518) on injectable RA medications (ETN, ADA, ANA, ABA, IFX, RIT): Group 1 – study ITT (n=340); Group 2 – study completer (n=244); Group 3 – specialty pharmacy-matched cohort (n=244); Group 4 – community pharmacy-matched cohort (n=244)b	0.67 year (2007–2008)	Mean PDC: The sum of the days’ supply for all claims during the post-identification period divided by 240 days	Mean PDC: Group 1 (83), Group 2 (89), Group 3 (81), Group 4 (60)
Bonafede et al^Citation34	Retrospective cohort	Truven Health MarketScan Commercial Claims and Encounters	RA patients (N=4,542): ETN + MTX (n=3,724), MTX + HCQ + SSZ (n=818)	1 year (2009–2013)	PDC ≥80%	ETN + MTX (28), ETN alone (50), MTX alone (45), MTX + HCQ + SSZ (18)
PsO studies
Sandoval et al^Citation35	Retrospective cohort	Wake Forest School of Medicine Department of Dermatology Clinic	PsO patients (N=45): UST 45 mg (n=26), UST 90 mg (n=19)	NR (2009–2013)	Proportion of injections within ±2-week window of the recommended dosing schedule calculated every 12 weeks	UST 45 mg median (100), mean (87); UST 90 mg median (80), mean (78)
Doshi et al^Citation36	Retrospective cohort	Medicare files	PsO patients (N=2,707): IFX (n=318), UST (n=280), ADA (n=1,084), ETN (n=1,025)	1 year (2009–2012)	PDC ≥80%	IFX (49), UST (43), ADA (41), ETN (29)
Bhosle et al^Citation37	Retrospective cohort	North Carolina Medicaid	PsO patients (N=186) prescribed biologic during study period (ALE, EFA, ETN)	0.50 year (2001–2004)	Proportion of days of supply for dispensed prescription medications vs usage	ALE (60), EFA (73), ETN (68)
Li et al^Citation38	Retrospective cohort	Truven Health MarketScan Commercial Claims and Encounter and the Medicare Supplemental and Coordination of Benefits databases	PsO patients (N=3,249) prescribed biologics between the study period dates: divided by PDC patterns, Group 1: 50%≥ PDC <75% (n=760); Group 2: PDC <25% (n=535); Group 3: 25%≥ PDC <50% (n=574); Group 4: PDC >75% (n=1,380)	1 year (2007–2011)	PDC-based categorizations	Continually high adherence, Groups 1–4: (6, 0, 0, 96); High then low adherence, Groups 1–4: (24, 1, 58, 0); Moderate then low adherence, Groups 1–4: (0, 98, 17, 0); Consistently moderate adherence, Groups 1–4: (71, 1, 25, 4)
Goren et al^Citation39	Web-based survey	US claims database: Diplomat Specialty Pharmacy	PsO patients (N=345) prescribed biologic between study period dates: ADA (n=262), UST (n=83)	NR (2009–2011)	Adherence: number of patients who never missed taking medication or injection	ADA (67), UST (88)
Kamangar et al^Citation40	Cross- sectional	UCSF PsO Center	PsO patients (N=106) previously treated with one or more biologic agents (ETN, ADA, ALE, EFA, IFX, UST, GOL)	NR (2010–2011)	Frequency of a patient missing a dose of biologic	Never/rarely missed (67), sometimes (27), often (6)
PsA study
Ellis et al^Citation32	Retrospective cohort	Truven database	PsA patients (N=325) with first or most recent prescription for GOL	NR (2008–2010)	Proportion of the number of refills occurring between 21 and 38 days from a previous fill divided by the total refill intervals	GOL (76)

Notes:

a Unless specified otherwise, MPR is based on the sum of days’ supply of the index treatment divided by duration of treatment. The 80% cutoff has been examined as an acceptable threshold in multiple studies assessing medication adherence. Unless specified otherwise, PDC is the percentage of days covered, based on days’ supply of prescription claims during which a patient has medication available during the post-index period. The 80% cutoff has been examined in multiple studies assessing medication adherence and accepted as an accurate threshold.

b The DTM ITT cohort consisted of all patients enrolled in the DTM ITT program who were continuously enrolled in the plan for the 4-month preidentification period and 8-month postidentification period. The DTM completer cohort consists of the subset of DTM ITT patients who completed the month 6 DTM consultation and who could be matched to patients in the community pharmacy and specialty pharmacy cohorts. The community pharmacy and specialty pharmacy cohorts consist of continuously enrolled patients who could be matched to the DTM completer patients.

Abbreviations: ABA, abatacept; ADA, adalimumab; ALE, alefacept; ANA, anakinra; DMARDs, disease-modifying antirheumatic drugs; DTM, drug therapy management; EFA, efalizumab; EMR, electronic medical record; ETN, etanercept; GOL, golimumab; HCQ, hydroxychloroquine; IFX, infliximab; ITT, intent-to-treat; KPSC, Kaiser Permanente Southern California; LF, leflunomide; MAX, Medicaid Analytic Extract; MPR, medication possession ratio; MTX, methotrexate; NR, not reported; PBM, pharmacy benefits management; PDC, percentage of days covered; PsA, psoriatic arthritis; PsO, psoriasis; RA, rheumatoid arthritis; RIT, rituximab; SSZ, sulfasalazine; TNFi, tumor necrosis factor alpha inhibitor; UCSF, University of California–San Francisco; US, United States; UST, ustekinumab; VA, Veterans Affairs.

Table 2 Medication persistence study characteristics and results

Study	Type of study	Source of patient sample	Patient population	Time period	Persistence definition	Persistence rates (%)
RA studies
Shim et al^Citation41	Cross- sectional	Proprietary administrative claims database	RA/PsA patients (N=15,834) with a biologic insurance claim on TOC, CER, ETN, ADA, and INF with continuous enrollment in health plan from index claim to 15 months post-claim	1 year (2012–2013)	Persistent patients are those with treatment length of at least 365 days after the index claim without a therapy gap or switch in therapy	Overall (67)
Erhardt et al^Citation22	Retrospective cohort	VA clinical and administrative data	RA patients (N=2,296); veterans transitioning from MTX monotherapy: MTX + TNFi (n=2,125), MTX + HCQ + SSZ (n=171)	1 year (2006–2012)	Persistent patients are those for whom the treatment continued over the 12-month period without a ≥90-day gap in refilling of drug	MTX + TNFi (45), MTX + HCQ + SSZ (18)
Li et al^Citation25	Retrospective cohort	MAX files	RA patients (N=2,638; new users of biologics): ETN (n=1,359), ANA (n=267), IFX (n=1,012)	1 year (2000–2002)	Persistent patients are those who did not have a 90-day continuous gap in therapy or switched from initiation of second biologic within 90 days of discontinuation date of index biologic and no evidence use of the second (switched to) biologic in 120 days before discontinuation of indexed biologic	ETN (53.8), ANA (7), IFX (53.7)
Grijalva et al^Citation30	Retrospective cohort	Tennessee Medicaid managed care program	RA patients (N=6,018) with previously filled regimen and a year of continuous health plan enrollment; biologics and MTX: IFX, ETN, ADA, ANA	NR (1995–2004)	Median persistence: time to cessation of therapy for at least 90 days without the addition of an alternate DMARD and time to switching to a different DMARD regimen	In months:a IFX (2.8), ETN (5.8), ADA (4.4); in months:a MTX + IFX (5.1), MTX + ETN (4.8), MTX + ADA (7.2), MTX + ANA (5.1)
Sauer et al^Citation42	Retrospective cohort	VHA	RA patients (N=10,719) with one biologic prescription during study period (new/experienced biologic users); new biologic users: ETN (n=2,109), ADA (n=2,035), IFX (n=263), RIT (n=277), ABA (n=25), GOL (n=20); biologic experienced: ETN (n=3,040), ADA (n=2,120), IFX (n=498), RIT (n=92), ABA (n=122), GOL (n=2)	1 year (2008–2011)	Persistent patients are those with no 45-day gap in index biologic therapy after the end of clinical benefit from the previous dose and who did not switch to another biologic	RA new biologic users: ETN (54), ADA (55), IFX (57), RIT (29), ABA (51), GOL (55); RA biologic experienced: ETN (61), ADA (61), IFX (76), RIT (38), ABA (62), GOL (0)
Gu et al^Citation43	Retrospective cohort	Healthcore integrated research database	RA patients (N=4,937) initiating first-line biologics (new biologic users): ABA (n=290), ADA (n=1,471), CER (n=132), ETN (n=2,331), GOL (n=184), IFX (n=529)	1 year (2009–2013)	Persistent patients are those with <45-day gap in days of supply on their index agent or without a biologic switch	ABA (45), ADA (42), CER (33), ETN (45), GOL (34), IFX (47)
Howe et al^Citation44	Retrospective cohort	Humana Commercial Claims	RA patients (N=1,445; new/experienced biologic users); new biologic users: ABA (n=42), ADA (n=238), ETN (n=280), GOL (n=10), RIT (n=26), IFX (n=71); biologic experienced: ABA (n=37), ADA (n=231), ETN (n=338), GOL (n=4), RIT (n=12), IFX (n=145)	1 year (2007–2012)	Persistent patients are those who continued on index biologics without a ≥45-day gap in therapy until the end of the follow-up period, without a switch to another biologic	New biologic users: ABA (41), ADA (43), ETN (46), GOL (20), RIT (42), IFX (41); biologic experienced: ABA (60), ADA (60), ETN (60), GOL (25), RIT (50), IFX (63)
Fisher et al^Citation45	Retrospective cohort	HIRD	RA patients (N=4,985), including patients who were new/experienced users of biologics; new biologic users: ETN (n=1,595), ADA (n=417), IFX (n=414); biologic experienced: ETN (n=1,203), ADA (n=507), IFX (n=849)	1 year (2007–2011)	Persistent patients are those who did not have 1) a number of days from index date to date of the first occurrence of a switch to another biologic DMARD, 2) a gap in index therapy of 45 days between the end of the day of supply of the previous prescription and the next prescription renewal for self-injected agents, and 3) 101 days from the previous infliximab infusion (8-week dosing interval plus the 45-day gap)	New biologic users: ETN (62), ADA (66), IFX (69); biologic experienced: ETN (89), ADA (94), IFX (96)
Greenberg et al^Citation46	Retrospective analysis from a prospective registry	Corrona registry	Newly TNFi prescribed (n=1,475 biologically naïve, n=616 first-time switchers, n=151 second-time or more switchers) RA patients (N=2,242); new biologic users: ADA (n=460), ETN (n=480), IFX (n=535); first- time switcher: ADA (n=311), ETN (n=139), IFX (n=166)	1 year and 2 years (2002–2008)	Time from initiation to discontinuation of the anti- TNF or to last follow-up visit; treatment persistence was estimated using survival analysis methods	New users year 1/2: ADA (68/53), ETN (72/53), IFX (76/63); first- time switchers year 1/2: ADA (57/42), ETN (60/41), IFX (65/43)
Tang et al^Citation47	Retrospective cohort	PharMetrics: managed-care integrated medical and pharmacy claims	RA patients (N=1,242) receiving biologic and MTX combination treatment with previously filled prescriptions; biologic and MTX: ADA (n=145), ETN (n=607), IFX (n=490)	1 year (2000–2005)	Persistence was defined as the number of days between the first and last anti-TNF treatment and was reported as a percentage of the 1-year period after treatment initiation	ADA (71), ETN (73), IFX (78)b
Yazici et al^Citation48	Retrospective cohort	PharMetrics managed-care integrated medical and pharmacy claims	RA patients (N=9,074) who had previously initiated biologic treatment with health plan eligibility 3 months prior to and 6 months after index; population in 2000: ETN (n=563), ADA (n=0), IFX (n=127); population in 2002: ETN (n=447), ADA (n=0), IFX (n=736); populationin 2004: ETN (n=1,326), ADA (n=666), IFX (n=706)	NR (2000–2005)	Persistent patients are considered persistent until a 30-day treatment gap after completion of prior subscription or a switch in biologic prior	In 2000: ETN (50), ADA (NA), IFX (65); in 2002: ETN (7), ADA (NA), IFX (35); in 2004: ETN (1), ADA (5), IFX (20)
Cannon et al^Citation49	Retrospective analysis from a prospective registry	VARA registry	RA-confirmed patients (N=563) on first TNFi therapy after March 17, 2003, and enrolled in the VA for at least 6 months prior to first TNFi prescription: ADA (n=204), ETN (n=290), IFX (n=69)	1 year, 5 years	The number of days from the course start date to course end date or the date of a switch to an alternative TNFi, whichever came first; treatment persistence was estimated using survival analysis methods	1 year: ADA (64), ETN (56), IFX (67); 5 years: ADA (25), ETN (18), IFX (21)
Markenson et al^Citation50	Retrospective analysis from a prospective registry	RADIUS 1 registry	Patients with first exposure to TNFi during the study (N=2,418, including patients who were biologic naïve and patients previously treated with a biologic agent); course 1: ETN (n=694), IFX (n=1,427), ADA (n=297); course 2: ETN (n=248), IFX (n=130), ADA (n=277)c	5 years (2001–2003)	Time from initiation of TNFi to discontinuation; treatment persistence was estimated using survival analysis methods	Course 1 rates for years 1–5: ETN (78, 66, 61, 53, 51); IFX (76, 65, 58, 51, 48); ADA (80, 65, 52, 48);d course 2 rates for years 1–3: ETN (74, 59, 56), IFX (77, 59, 50), ADA (69, 52, 46)
Agarwal et al^Citation51	Prospective cohort	BRASS	RA patients (N=503) without a previous specific treatment protocol (ETN, ADA, IFX)	3.25 years	Persistent patients are those who did not discontinue the TNFi they reported using and remained on the same TNFi	Overall (58)
Stockl et al^Citation33	Prospective cohort	PBM DTM program	RA patients (N=518) on injectable RA medications (ETN, ADA, ANA, ABA, IFX, RIT): Group 1 – study ITT (n=340); Group 2 – study completer (n=244); Group 3 – specialty pharmacy (n=244); Group 4 – community pharmacy (n=244)	0.67 year (2007–2008)	Persistent patients are those without a 30-day gap between depletion date (fill date plus days’ supply) for the last filled prescription and the end of the post-identification period or switching from index injectable RA medication to another injectable RA medication	Group 1 (77), Group 2 (87), Group 3 (73), Group 4 (52)
Agarwal et al^Citation52	Retrospective chart review	Hospital infusion center pharmacy and EMRs	RA patients (N=183) receiving at least one infusion of IFX	5 years (1999–2003)	Persistent patients are those who did not discontinue treatments	Overall (33)
Bonafede et al^Citation34	Retrospective cohort	Truven Health MarketScan Commercial Claims and Encounters	RA patients (N=4,542): ETN + MTX (n=3,724), MTX + HCQ + SSZ (n=818)	1 year (2009–2013)	Persistent patients are those with no treatment gap of >45 days for any drug and no addition or switching to other DMARDs	ETN + MTX (29); MTX + HCQ + SSZ (23)
Bolge et al^Citation53	Cross- sectional	National Health and Wellness Surveys and the Light Speed Research Ailment Panel	RA existing biologic users (N=250)	NA (2008–2010)	Persistent patients are those who did not discontinue biologics in the 12-month period	Overall (51) ADA (61) CER (90) ETN (66) GOL (92)
PsO studies
Bonafede et al^Citation54	Retrospective cohort	Truven Health Analytics Market Scan Commercial Claims and Encounters	PsO patients (N=2775; new/experienced biologic users): ADA (n=1,166), ETN (n=1,609)	1 year (2005–2010)	Persistent patients are those who remained on biologic and did not switch or have a therapy gap of ≥45 days	ADA (57), ETN (46)
Sauer et al^Citation42	Retrospective cohort	VHA	PsO patients (N =3,426) with one biologic prescription during study period (new/experienced biologic users); new biologic users: ADA (n =924), ETN (n=1,136), INF (n =20); biologic experienced: ADA (n=260), ETN (n =1,047), INF (n=16)	1 year (2008–2011)	Persistent patients are those who continued on index biologics without a ≥45-day gap in therapy until the end of the follow-up period, without a switch to another biologic	New biologic users: ADA (51), ETN (47), INF (55); biologic experienced: ADA (58), ETN (50), INF (75)
Howe et al^Citation44	Retrospective cohort	Humana Commercial Claims	PsO patients (N=576; new/experienced biologic users); new biologic users: ADA (n=126), ETN (n=155); biologic experienced: ADA (n=69), ETN (n=214)	1 year (2007–2012)	Persistent patients are those who continued on index biologics without a ≥45-day gap in therapy until the end of the follow-up period, without a switch to another biologic	New biologic users: ADA (50), ETN (34); biologic experienced: ADA (62), ETN (48)
Chastek et al^Citation55	Retrospective cohort	National US health plan OptumInsight	PsO patients (N=827; new users), ≥1 medical claim with a diagnosis for PsO (ICD-9 code 696.1) from baseline through 30 days after the index date: ETN (n=330), ADA (n=497)	1 year (2008)	Persistent patients are those with no gaps in therapy ≥60 days	ETN (42), ADA (40)
Feldman et al^Citation56	Retrospective cohort	MarketScan Commercial Encounters Database	PsO patients (N=4,309) with ≥2 claims for biologic agents: ETN (n=2,452), ADA (n=1,662), UST (n=195)	1 year (2007–2012)	Persistent patients are those with no treatment gaps that exceeded 4–18 weeks, dependent upon the biologic prescribed	ETN (19), ADA (53); UST (71)
Cao et al^Citation57	Retrospective cohort	Truven Health MarketScan Commercial Claims and Encounters	PsO patients (N=1,152) with ≥1 nondiagnostic medical claim or prescription claim indicating UST treatment: UST (n=1,000)	1 year (2009–2010)	Persistent patients are those with continual usage over 130 days	UST (81)
PsA studies
Shim et al^Citation41	Cross- sectional	Proprietary administrative claims database	RA/PsA patients (N=15,834) with a biologic insurance claim on TOC, CER, ETN, ADA, and INF with continuous enrollment in health plan from index claim to 15 months post-claim	1 year (2012–2013)	Persistent patients are those with a treatment length of at least 365 days after the index claim without a therapy gap or switch in therapy	Overall (67)
Sauer et al^Citation42	Retrospective cohort	VHA	PsA patients (N=875) with one biologic prescription during study period (new/experienced biologic users); new biologic users: ADA (n=924), ETN (n=1,136), INF (n=20); biologic experienced: ADA (n=260), ETN (n=1,047), INF (n=16)	1 year (2008–2011)	Persistent patients are those who continued on index biologics without a ≥45-day gap in therapy until the end of the follow-up period, without a switch to another biologic	New biologic users: ADA (56), ETN (51), INF (74); biologic experienced: ADA (56), ETN (58), INF (79)
Mease et al^Citation58	Retrospective analysis from a prospective registry	Corrona registry	PsA patients (N=519; new users) with 6 months post-follow-up after index treatment: ADA (n=214), ETN (n=155), IFX (n=110)	1 year (2004–2012)	Median persistence: the length of time that patients with PsA maintained their initial biologic therapy	ADA: mono (2.4 years), combo (2.4 years); ETN: mono (3.9 years), combo (1.6 years); IFX: mono (1.4 years), combo (NR)
Chastek et al^Citation59	Retrospective cohort	OptumInsight Life Sciences Research Database	PsA patients (N=346) with one previous claim and continuously enrolled in health plan: ADA (n= 144), ETN (n=202)	ADA: 1.2 years; ETN: 1 year (2006–2008)	Persistent patients are those with continuous use of index medication without gaps in therapy of at least 60 days	ADA (50), ETN (45)
Mixed studye
Bonafede et al^Citation54	Retrospective cohort	Truven Health Analytics Market- Scan Commercial Claims and Encounters	PsO/PsA (N=481) patients who had initiated biologic therapy: ADA (n=235), ETN (n=246)	1 year (2005–2010)	Persistent patients are those who did not have to switch to another TNFi or have a gap in therapy of ≥45 days over the run-out of the fill	PsA and PsO: ADA (60), ETN (58)

Notes:

a Median months of persistence.

b Percentage of days of being persistent.

c First-course therapy was defined as the first exposure to an anti-TNF agent at any time during the study. Second-course therapy was defined as initiation of any anti-TNF agent following the first discontinuation.

d Data for adalimumab was reported up to 4 years only.

e Data combined for multiple disease states (rather than separated by disease state).

Abbreviations: ABA, abatacept; ADA, adalimumab; ANA, anakinra; BRASS, Brigham RA Sequential Study; CER, certolizumab pegol; DMARD, disease-modifying antirheumatic drug; DTM, drug therapy management; EMR, electronic medical record; ETN, etanercept; GOL, golimumab; HCQ, hydroxychloroquine; HIRD, HealthCore Integrated Research Database; ICD-9, International Classification of Diseases, Ninth Revision; INF or IFX, infliximab; ITT, intent-to-treat; MAX, Medicaid Analytic Extract; MTX, methotrexate; NR, not reported; PBM, pharmacy benefits management; PsA, psoriatic arthritis; PsO, psoriasis; RA, rheumatoid arthritis; RADIUS, Rheumatoid Arthritis Disease-Modifying Anti-Rheumatic Drug Intervention and Utilization Study; RIT, rituximab; SSZ, sulfasalazine; TNFi, tumor necrosis factor alpha inhibitor; TOC, tocilizumab; US, United States; UST, ustekinumab; VA, Veterans Affairs; VARA, Veterans Affairs Rheumatoid Arthritis; VHA, Veterans Health Administration.

Table 3 Risk of bias assessmenta

Author, year	1	2	3	4	5	6	7	8	9	10	11	12
Chu et al,^Citation21 2015	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	High
Erhardt et al,^Citation22 2015	Low	Low	Low	Low	NA	Low	Low	NA	Low	High	Low	Low
Oladapo et al,^Citation23 2014	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	Low
Tkacz et al,^Citation24 2014	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	Unclear
Li et al,^Citation38 2014	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Unclear	Low
Borah et al,^Citation26 2009	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	Low
Grijalva et al,^Citation27 2010	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low
Harley et al,^Citation28 2003	Low	Low	Low	Low	Low	Low	Low	High	Low	Unclear	Low	Unclear
Curkendall et al,^Citation29 2008	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	High
Grijalva et al,^Citation30 2007	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	Unclear
Barlow et al,^Citation31 2012	Low	Low	Low	Low	Low	Low	Low	Unclear	Low	High	Low	High
Ellis et al,^Citation32 2014	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	High
Stockl et al,^Citation33 2010	Low	Low	Low	Low	Low	Low	Low	Unclear	Low	High	Low	Unclear
Bonafede et al,^Citation54 2013	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low
Sandoval et al,^Citation35 2013	Low	Low	Low	Low	Unclear	Low	Low	Low	Low	High	Low	Unclear
Doshi et al,^Citation36 2015	Low	Low	Low	Low	Unclear	Low	Low	Low	Low	No	Low	Unclear
Bhosle et al,^Citation37 2006	NA	NA	NA	Low	NA	Low	NA	Low	Low	Low	Low	Low
Li et al,^Citation25 2010	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	Low
Goren et al,^Citation39 2016	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low
Kamangar et al,^Citation40 2013	NA	NA	NA	Low	NA	Low	NA	Low	Low	Low	Unclear	Low
Shim et al,^Citation41 2015	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	High
Sauer et al,^Citation42 2016	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	High
Gu et al,^Citation43 2015	Low	Low	Low	Low	Low	Low	Low	Low	High	High	Low	High
Howe et al,^Citation44 2014	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	Unclear
Fisher et al,^Citation45 2013	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	High
Greenberg et al,^Citation46 2012	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low
Tang et al,^Citation47 2008	Low	Low	Low	Low	Low	Low	Low	High	Low	High	Low	Unclear
Yazici et al,^Citation48 2009	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	Low
Cannon et al,^Citation49 2014	Low	Low	Low	Low	Low	Low	Low	Unclear	Low	High	Low	Unclear
Markenson et al,^Citation50 2011	Low	Low	Low	Low	Low	Low	Unclear	Unclear	Low	Low	Low	High
Agarwal et al,^Citation51 2008	Low	Low	Low	Low	Low	Low	Unclear	Low	Low	Low	Low	Low
Bonafede et al,^Citation34 2015	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	High
Agarwal et al,^Citation52 2005	NA	NA	NA	Low	NA	Low	NA	Low	Low	Low	Low	Low
Chastek et al,^Citation55 2013	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low
Feldman et al,^Citation56 2015	Low	Low	Low	Low	Low	Low	Low	Low	Low	High	Low	Low
Cao et al,^Citation57 2015	NA	NA	NA	Low	NA	Low	NA	Unclear	Low	Low	Low	High
Mease et al,^Citation58 2015	Low	Low	Low	Low	Unclear	Low	Low	Low	Low	Low	Unclear	Low
Chastek et al,^Citation59 2012	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low
Bolge et al,^Citation53 2015	Low	Low	Low	Low	Low	Low	NA	Low	Low	Low	Low	Low
Kwiatkowski et al,^Citation60 2015	NA	NA	NA	Low	Low	Low	NA	Low	Unclear	Low	Low	Low
Zhang et al,^Citation61 2013	Low	Low	Low	Unclear	Low	Low	Low	Low	Low	Low	Low	High
Menter et al,^Citation62 2014	Low	Low	Low	Unclear	Low	Low	Low	Low	Low	Low	Low	Low
Zhang et al,^Citation63 2015	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low	Low

Notes:

a The table answers whether there is a low, high, or unclear risk of bias for these questions: 1. Do the inclusion/exclusion criteria vary across the comparison groups of the study? 2. Does the strategy for recruiting participants into the study differ across groups? 3. Is the selection of the comparison group inappropriate, after taking into account feasibility and ethical considerations? 4. Does the study fail to account for important variations in the execution of the study from the proposed protocol? 5. Was the outcome assessor not blinded to the intervention or exposure status of participants? 6. Were valid and reliable measures implemented consistently across all study participants used to assess inclusion/exclusion criteria, intervention/exposure outcomes, participant health benefits and harms, and confounding? 7. Was the length of followup different across study groups? 8. In cases of high loss to follow-up (or differential loss to follow-up), was the impact assessed (eg, through sensitivity analysis or other adjustment method)? 9. Are any important primary outcomes missing from the results? 10. Are any important harms or adverse events that may be a consequence of the intervention/exposure missing from the results? 11. Are results believable, taking study limitations into consideration? 12. Were important confounding variables not taken into account in the design and/or analysis (eg, through matching, stratification, interaction terms, multivariate analysis, or other statistical adjustment such as instrumental variables)?

Abbreviation: NA, not applicable.

Embase 1974 to 2015 December 28, 2015 using OvidSp

1	*rheumatoid arthritis/	97,740
2	*rheumatoid nodule/	651
3	(rheumatoid adj nodule).ti,ab.	295
4	(arthritis adj2 rheumat$).ti,ab.	119,688
5	RA.ti,ab.	85,007
6	*psoriasis/	31,038
7	psoria$.ti,ab.	52,099
8	*psoriatic arthritis/	6,451
9	psoriatic arthrit$.ti,ab.	9,783
10	or/1-9	224,711
11	*medication compliance/	3,158
12	*patient compliance/	19,028
13	(cooperat$ or co-operat$).ti,ab.	137,785
14	*treatment refusal/	3,763
15	(treatment adj2 refusal).ti,ab.	652
16	*patient dropouts/	107
17	patient dropout$.ti,ab.	212
18	(uncooperat$ or unco-operat$).ti,ab.	1,488
19	(patient adj perspective$).ti,ab.	2,682
20	(patient adj attitude$).ti,ab.	1,047
21	(patient adj experience$).ti,ab.	15,219
22	continuation rate$.ti,ab.	1,162
23	(adher$ adj5 (regimen$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	41,915
24	(complian$ adj5 (regimen$ or patient$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	50,669
25	(persist$ adj5 (regimen$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	31,812
26	((nonadher$ or non-adher$ or non adher$) adj5 (regimen$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	6,231
27	((nonpersist$ or non-persist$ or non persist$) adj5 (regimen$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	233
28	((noncomplian$ or non-complian$ or non complian$) adj5 (patient$ or regimen$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	7,993
29	(assessment adj5 (adher$ or complian$ or persist$)).ti,ab.	3,684
30	(assessment adj5 (nonadher$ or non-adher$ or non adher$)).ti,ab.	85
31	(assessment adj5 (noncomplian$ or non-complian$ or non complian$)).ti,ab.	81
32	(assessment adj5 (nonpersist$ or non-persist$ or non persist$ or nonpersist$)).ti,ab.	5
33	or/11-32	294,808
34	10 and 33	3,614
35	limit 34 to (conference abstract or conference paper or conference proceeding or “conference review” or editorial or letter or “review”)	1,764
36	34 not 35	1,850
37	limit 36 to human	1,478

Ovid Medline (R) in-process and other non-indexed citations and Ovid and Medline (R) 1946 – December 28, 2015 using OvidSp

1	*Arthritis, Rheumatoid/	69,229
2	*Rheumatoid Nodule/	567
3	(rheumatoid adj nodule).ti,ab.	240
4	(arthritis adj2 rheumat$).ti,ab.	86,167
5	RA.ti,ab.	56,769
6	*Psoriasis/	23,577
7	psoria$.ti,ab.	35,733
8	psoriatic arthrit$.ti,ab.	5,659
9	*Arthritis, Psoriatic/	3,171
10	or/1-9	161,396
11	*Medication Adherence/	6,402
12	*Patient Compliance/	20,742
13	(adher$ adj5 (regimen$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	27,924
14	(complian$ adj5 (regimen$ or patient$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	32,328
15	(persist$ adj5 (regimen$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	23,065
16	cooperat$ or co-operat$).ti,ab.	118,393
17	*Treatment Refusal/	5,526
18	(treatment adj2 refusal).ti,ab.	514
19	*Patient Dropouts/	2,516
20	patient dropout$.ti,ab.	172
21	((nonadher$ or non-adher$ or non adher$) adj5 (regimen$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	4,056
22	((nonpersist$ or non-persist$ or non persist$) adj5 (regimen$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	131
23	((noncomplian$ or non-complian$ or non complian$) adj5 (patient$ or regimen$ or medication$ or treatment$ or therap$ or drug$ or intervention$ or biologic$)).ti,ab.	5,319
24	(uncooperat$ or unco-operat$).ti,ab.	1,188
25	(patient adj perspective$).ti,ab.	1,878
26	(patient adj attitude$).ti,ab.	811
27	(patient adj experience$).ti,ab.	10,173
28	continuation rate$.ti,ab.	1,142
29	(assessment adj5 (adher$ or complian$ or persist$)).ti,ab.	2,418
30	(assessment adj5 (nonadher$ or non-adher$ or non adher$)).ti,ab.	57
31	(assessment adj5 (noncomplian$ or non-complian$ or non complian$)).ti,ab.	49
32	(assessment adj5 (nonpersist$ or non-persist$ or non persist$ or nonpersist$)).ti,ab.	4
33	or/11-32	235,799
34	10 and 33	2,041
35	limit 34 to (case reports or comment or in vitro or lectures or letter or “review”)	467
36	34 not 35	1,574
37	limit 36 to humans	1,250

Cochrane, December 28, 2015 (CENTRAL only)

1	MeSH descriptor: [Arthritis, Rheumatoid] explode all trees	4,206
2	MeSH descriptor: [Rheumatoid Nodule] explode all trees	11
3	rheumatoid next nodule*:ti,ab,kw (Word variations have been searched)	17
4	arthritis near/3 rheumat*:ti,ab,kw (Word variations have been searched)	7,762
5	RA:ti,ab,kw (Word variations have been searched)	4,379
6	MeSH descriptor: [Psoriasis] explode all trees	1,916
7	psoria*:ti,ab,kw (Word variations have been searched)	4,176
8	MeSH descriptor: [Arthritis, Psoriatic] explode all trees	199
9	psoriatic arthrit*:ti,ab,kw (Word variations have been searched)	551
10	MeSH descriptor: [Medication Adherence] explode all trees	1,141
11	MeSH descriptor: [Patient Compliance] explode all trees	9,064
12	adher* near/5 (regimen* or medication* or treatment* or therap* or drug* or intervention* or biologic*):ti,ab,kw (Word variations have been searched)	5,854
13	((complian* or complian* or complian*) near/5 (regimen* or medication* or treatment* or therap* or drug* or intervention* or biologic*)):ti,ab,kw (Word variations have been searched)	8,236
14	((persist*) near/5 (regimen* or medication* or treatment* or therap* or drug* or intervention* or biologic*)):ti,ab,kw (Word variations have been searched)	3,335
15	(cooperat* or co-operat*):ti,ab,kw (Word variations have been searched)	6,506
16	MeSH descriptor: [Treatment Refusal] explode all trees	262
17	treatment near/2 refusal:ti,ab,kw (Word variations have been searched)	443
18	MeSH descriptor: [Patient Dropouts] explode all trees	1,589
19	patient dropout*:ti,ab,kw (Word variations have been searched)	3,269
20	((nonadher* or non-adher* or non adher*) near/5 (regimen* or medication* or treatment* or therap* or drug* or intervention* or biologic*)):ti,ab,kw (Word variations have been searched)	440
21	((noncomplian* or non-complian* or non complian*) near/5 (patient* or regimen* or medication* or treatment* or therap* or drug* or intervention* or biologic*)):ti,ab,kw (Word variations have been searched)	785
22	((nonpersist* or non-persist* or non persist*) near/5 (regimen* or medication* or treatment* or therap* or drug* or intervention* or biologic*)):ti,ab,kw (Word variations have been searched)	29
23	(uncooperat* or unco-operat*):ti,ab,kw (Word variations have been searched)	134
24	(assessment near/5 (adher* or complian* or persist*)):ti,ab,kw (Word variations have been searched)	1,751
25	(assessment near/5 (nonadher* or non-adher* or non adher*)):ti,ab,kw (Word variations have been searched)	3
26	(assessment near/5 (noncomplian* or non-complian* or non complian*)):ti,ab,kw (Word variations have been searched)	8
27	(assessment near/5 (nonpersist* or non-persist* or non persist*)):ti,ab,kw (Word variations have been searched)	0
28	(patient next perspective*):ti,ab,kw (Word variations have been searched)	252
29	patient next attitude*:ti,ab,kw (Word variations have been searched)	1,001
30	patient next experience*:ti,ab,kw (Word variations have been searched)	4,444
31	continuation rate*:ti,ab,kw (Word variations have been searched)	1,015
32	#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9	13,154
33	#10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31	36,736
34	#32 and #33	552
35	MeSH descriptor: [Arthritis, Rheumatoid] this term only	4,063
36	MeSH descriptor: [Rheumatoid Nodule] this term only	11
37	MeSH descriptor: [Psoriasis] this term only	1,749
38	MeSH descriptor: [Arthritis, Psoriatic] this term only	199
39	MeSH descriptor: [Medication Adherence] this term only	1,141
40	MeSH descriptor: [Patient Compliance] this term only	7,978
41	MeSH descriptor: [Treatment Refusal] this term only	262
42	MeSH descriptor: [Patient Dropouts] this term only	1,589
43	#3 or #4 or #5 or #7 or #9 or #35 or #36 or #37 or #38	13,016
44	#12 or #13 or #14 or #15 or #17 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #39 or #40 or #41 or #42	36,736
45	#43 and #44	549

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