Introduction
Methods
Search Strategy and Study Selection
Definitions Used to Align Measures of Persistence and Compliance
-
Compliance: The extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen.
-
Persistence: The duration of time from initiation to discontinuation of therapy.
Compliance with Ethics Guidelines
Results
Search Results
Inclusion criteria |
Studies in the English language Real-world data studies, such as observational studies using databases and registries, pragmatic clinical trials, phase IV trials/post-marketing open-label/’off-label’ studies, patient and population surveys, chart review, economic models based on real-world data Publications based on original research Interventions including TNFi, other biologics with alternative MOA or JAK inhibitor treatment Patients studied with any of the following diseases: RA, PsO, PsA, JIA, AS, axSpA, nr-axSpA, uveitis, CD and pediatric CD Treatment persistence, adherence and/or compliance was included as an outcome |
Exclusion criteria |
Interventional studies Review and meta-analyses on RCTs that do not include RWE based on the abstract In vitro/pre-clinical studies Non-human studies Economic models based on data other than cohorts or other RWE Guidelines, letters, editorials Review articles; however, recent (< 2 years old) key reviews were marked and cross-checked Studies identified during the gray literature search were excluded unless they came from Australia, Brazil, Canada, China, France, Germany, India, Italy, Japan, Korea, Russia, Spain, Turkey, the UK or the USA Clinical efficacy and safety studies in relation to biologic switching Clinical safety studies with only discontinuation data related to adverse events Studies only reporting the number of patients who switched/discontinued biologic treatment |
Overview of Compliance and Persistence with Biologic Therapy
Compliance with TNFi Therapy
Country | Data source | Time point | Treatment | |||
---|---|---|---|---|---|---|
Adalimumab | Etanercept | Infliximab | Golimumab | |||
USA | Registries | 1 year [82] | – | – | 65.7% (CD) | – |
Claims data | 70.0%a (RA) | 32%a (RA) 61.2%a (RA) | 43%a (RA) 73% (CD) | 81.2a (RA) | ||
Medical records | 1 year [100] | – | – | 96% (CD)b | – |
Persistence with TNFi Therapy
Country | Data source | Time point | Treatment | ||||
---|---|---|---|---|---|---|---|
Adalimumab | Certolizumab pegol | Etanercept | Infliximab | Golimumab | |||
Austria | Claims | 1 year [46] | 70% (AS) | – | 83% (AS) | 71% (AS) | – |
2 years [46] | 55% (AS) | – | 58% (AS) | 54% (AS) | – | ||
Belgium | Registries | 5 years [89] | – | – | – | – | – |
Medical records | 7 years [42] | – | – | – | 36% (RA) | – | |
Denmark | Registries | – | – | 73% (RA) | 71% (RA) 58% (PsA) | – | |
Finland | Medical records | 1 year [66] | – | – | 83% (JIA) | 80% (JIA) | – |
2 years [66] | – | – | 68% (JIA) | 68% (JIA) | – | ||
4 years [66] | – | – | 61% (JIA) | 48% (JIA) | – | ||
France | Medical records | 86% (RA) 68.2% (RA and SpA) | – | 87% (RA) 76% (AS) 63.9% (RA and SpA) | 68% (RA) 78.9% (AS) 63.2% (RA and SpA) | – | |
66% (RA) 60.2% (RA and SpA) | – | 68% (RA) 50.8% (RA and SpA) | 46% (RA) 83% (AS) 47.5% (RA and SpA) | – | |||
50 months [91] | – | – | 50% (RA) | – | – | ||
Greece | Registries | 1 year | 67% (RA) | – | 68% (RA) | 64% (RA) | – |
5 years | 43% (RA) | – | 49% (RA) | 31% (RA) | – | ||
Medical records | 1 year [93] | 83.7% (RA) | – | 70% (RA) | 82.9–84.5% (RA) | – | |
44.9% (RA) 50% (PsA) | – | 76% (PsA) | 56.7% (PsA) | – | |||
7 years [93] | – | – | – | 32.9% (RA) | – | ||
Iceland | Registries | 1 year [26] | – | – | – | 66% (PsA) | – |
Italy | Registries | 3 years [94] | – | – | – | 58% (RA) | – |
4 years [95] | 36.4% (RA) | – | 51% (RA) | 37.6% (RA) | – | ||
5 years [94] | – | – | – | 41.1% (RA) | – | ||
Medical records | 65.38% (PsO) 79% (RA) | – | 65.65% (PsO) 76% (RA) | 71.43% (PsO) | – | ||
46.55% (PsO) 60% (RA) | – | 37.07% (PsO) 61% (RA) | 46.07% (PsO) | – | |||
4 years [96] | 27% (RA) | – | 21% (RA) | – | – | ||
Japan | Registries | 1 year [97] | – | – | 84.6% (RA) | – | – |
2 years [54] | – | – | 72% (RA) | – | – | ||
3 years [54] | – | – | 67% (RA) | – | – | ||
Medical records | 1 year [98] | 78.2% (RA) | – | 85.9% (RA) | 73.1% (RA) | – | |
2.5 years [98] | 54.5% (RA) | – | 77.7% (RA) | 47.2% (RA) | – | ||
5 years [98] | – | – | 61.9% (RA) | 29.8% (RA) | – | ||
The Netherlands | Registries | 1 year [27] | 74% (PsO) | – | 68% (PsO) | – | – |
Spain | Registries | 1 year [68] | 67–87% (RA, AS, PsA, JIA, etc.) | – | 76–88% (RA, AS, PsA, JIA, etc.) | – | – |
Sweden | Registries | 1 year [34] | 57% (RA, PsA and AS) | 55% (RA, PsA, AS) | 56% (RA, PsA, AS) | – | 58% (RA, PsA, AS) |
2 years [34] | 40% (RA, PsA and AS) | 40% (RA, PsA and AS) | 39% (RA, PsA and AS) | – | 46% (RA, PsA and AS) | ||
3 years [34] | 33% (RA, PsA and AS) | 33% (RA, PsA and AS) | 33% (RA, PsA and AS) | – | 40% (RA, PsA and AS) | ||
Taiwan | Medical records | 1 year [57] | 83.3% (RA) | – | 91.1% (RA) | – | – |
UK | Registries | 1 year [22] | 91% (PsA) | – | 86% (PsA) | 71% (PsA) | – |
2 years [22] | 70% (PsA) | – | 79% (PsA) | 52% (PsA) | – | ||
3 years [22] | 66% (PsA) | – | 65% (PsA) | 43% (PsA) | – | ||
USA | Claims | 47% (RA, PsO, PsA and AS) 45% (PsA) 66-94% (RA) | – | 42% (RA, PsO, PsA and AS) 50% (PsA) 62.2-89.2% (RA) | 56% (RA, PsO, PsA and AS) 68.9-96.4% (RA) | – |
Factors Leading to Suboptimal Persistence and Compliance
Impact of Drug Delivery Devices and Patient Support Services on Compliance and Persistence
Study | Patients | Type of device | Key outcome |
---|---|---|---|
Treatment devices | |||
Borrás-Blasco [76] | Phase 1: N = 55 (RA: 29, PsA: 17, AS: 9) Phase 2: N = 51 (4 lost) | Adalimumab: Prefilled syringe vs. auto-injection pen | Patients reported 100% adherence to treatment with the auto-injection pen over an 8-week period |
Borrás-Blasco [74] | RA, PsA, AS patients Phase 1: N = 82 Phase 2: N = 104 | Etanercept: Prefilled syringe vs. auto-injection pen | Patients reported > 95% adherence to treatment with the etanercept auto-injection pen over an 8-week period |
Calip [101] | N = 53,477 (etanercept: 26,996; adalimumab: 22,210; certolizumab pegol: 1601; golimumab: 2670) | Mixed injection devices, self-administered | Compliant: year 1 (36.5%), year 2 (33.6%), year 3 (28.8%) Persistent: year 1 (82.6%), year 2 (80.5%), year 3 (80.1%) |
Schulze-Koops [77] | RA (N = 3280) | Golimumab (SmartJect® auto-injection device) (Janssen Biotech Inc, Horsham, PA, USA) | 91.7% completed 6 months of treatment |
Patient support services | |||
Liu et al. [78] | Responder, patients receiving adalimumab: (N = 299) RA (36%), CD (24%), PsO (22%), PsA (22%), UC (9%), AS (7%) | Adalimumab (myHUMIRA®) (AbbVie, North Chicago, IL, USA) PSP | Patients in PSP vs. non-PSP: Intention to be non-compliant: 3.6 vs. 3.2 (p < 0.001) Therapy satisfaction: 4.1 vs. 3.5 (p < 0.001) Perception of therapy as beneficial: 3.6 vs. 3.2 (p < 0.001) |
Clinical and Economic Consequences of Treatment Non-Compliance and Non-Persistence
Study | Type of study | Data source, country | Clinical and/or economic implications | Compliance | Persistence |
---|---|---|---|---|---|
An [102] | Multicenter observational cross-sectional study | Questionnaire China | A significantly larger proportion of patients with ≥ 12 months bDMARD therapy achieved treatment target (low disease activity or remission) compared with patients with < 12 months Proportion of patients achieving treatment target was significantly lower in patients with < 3 months bDMARDs with 3.0–5.9 months bDMARDs | X | |
Billioud [73] | Observational multicenter study (medical records from 4 university hospitals) | France | Predictors of non-compliance include having at least one relapse in the past 12 months, having a disease duration over 93 months, and receiving adalimumab 80 mg every other week (two injections at once) The main reasons for delay were forgetfulness, travel and infection | X | |
Borah [41] | Retrospective cohort analysis | Claim data USA | Among non-compliant patients, the number of inpatient visits was significantly higher for etanercept users vs. adalimumab users Etanercept users had significantly lower RA-related pharmacy costs and RA-related total costs than adalimumab users | X | |
Bluett [80] | Multicenter prospective observational cohort study (Biologics in RA Genetics and Genomics Study Syndicate study) | UK | Non-adherence was significantly associated with a lower DAS28 response following 6 months of subcutaneous TNFi therapy | X | |
Carter [81] | Retrospective observational study | IMS PharMetrics database USA | Mean hospital costs were significantly lower for compliant patients vs. non-compliant patients, with compliant patients requiring fewer emergency room visits and less hospitalization Among those hospitalized, compliant patients spent fewer days in the hospital vs. non-compliant patients | X | |
Courvoisier [103] | Cross-sectional multicenter study | Registries Sweden, Czech Republic, Denmark, Italy, Norway, France Portugal, Canada, Switzerland | Proportion of patients with EULAR good or moderate response rate (Lundex corrected) at 1 year was higher among ‘rapid responders’ | X | |
Dalen [34] | Retrospective observational study | Swedish Prescribed Drug Register Sweden | Mean total costs prior to and post-treatment initiation decreased in persistent patients, and increased in non-persistent patients | X | |
Degli Esposti [86] | Observational retrospective cohort | 3 databases of Italian Local Health Authorities Italy | The treatment costs for patients switching from initial treatment during the first year of follow-up were higher than for patients who did not switch (€12,710 vs. €11,332) For patients not persistent with their initial drug, other healthcare costs (hospitalizations, specialist care, etc.) were significantly higher than those for persistent patients (€1,088 vs. €375) | X | |
Foster [104] | Retrospective observational cohort study | MarketScan claims database USA | Total healthcare costs were lower in non-treatment-regimen failures than in treatment-regimen failures ($6,637 vs. $8,024; p = 0.002) Psoriasis-related total healthcare costs were higher in non-treatment-regimen failures than in treatment-regimen failures ($25,286 vs. $19,625; p < 0.001) | X | |
Harnett [84] | Retrospective cohort analysis | Truven Marketscan, Commercial Claims and Encounters and Medicare Supplemental Databases USA | Discontinuers had significantly lower RA-related costs compared with those classified as switchers | X | |
Inzinger [105] | Observational retrospective multicenter study | Psoriasis Registry Austria | Drug survival correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab | X | |
Kane [82] | Observational study | Integrated Health Care Information Service (IHCIS) National Managed Care Benchmark Database USA | Adjusted medical and hospitalization costs for non-compliant patients were greater compared with compliant patients Etanercept had the lowest 1-year index biologic cost per effectively treated patient, followed by adalimumab, infliximab, abatacept, and rituximab | X | |
Lequerre [106] | Observational retrospective cohort | France | A greater proportion of patients were considered responders (DAS28 improvement > 1.2) after the second biologic agent (p < 0.01) DAS28 improvements were more pronounced with the second immunotherapy than the first (p < 0.001), regardless of type of failure or switching order | X | |
Sauer [107] | Observational retrospective cohort | Corporate Data Warehouse USA | Among the patients categorized as ineffectively treated, the most common criterion for failure was low adherence, followed by addition of a new DMARD, having a new or increased oral glucocorticoid dose, switching biologics, increasing the biologic dose and having > 1 glucocorticoid injection | X | |
Stein [83] | Retrospective observational study | Medical records USA | The prior irregular group (no loading, gap in therapy > 8 weeks prior to or during maintenance infliximab) showed higher rates of hospitalizations and surgical hospitalizations compared with the scheduled maintenance group (maintenance infliximab infusions every ≤ 8 weeks after loading dose) at Year 3 The prior irregular group had higher excess costs per patient during the 3rd year of infliximab maintenance therapy, despite both groups receiving scheduled maintenance therapy | X | |
Svedbom [108] | Retrospective administrative register study | Registries Sweden | In patients who remained persistent with treatment for at least 6 months, the annualized costs incurred with first-line TNFi were lower than costs incurred with second-line TNFi During this period, mean TNFi costs were lower in second-line patients compared with first-line patients Excluding TNFi costs, there was no statistically significant difference in costs between first- and second-line patients in the 6 months preceding indexation | X | |
Tang [85] | Retrospective observational study | IMS PharMetrics database USA | The > 80% persistence cohort had higher total healthcare costs, driven by higher pharmacy costs The > 80% persistence cohort had lower medical (non-pharmacy) healthcare costs | X |