Table 2.
Summary of included studies
| References | Study design (database) | Patients (N) | Dose adjustment definition | Treatments | Dose escalation (%) | Dose reduction (%) |
|---|---|---|---|---|---|---|
| Bewley (UK) [12] | Retrospective cohort study (Quintiles IMS Hospital Treatment Insights database) | 362 | > 30% increase in the average daily dose or decrease in the dosing interval compared with the posology in UK SPC | ETA (n = 60) | 20 | NR |
| UST (n = 44) | 18 | NR | ||||
| INF (n = 83) | 28 | NR | ||||
| ADA (n = 175) | 14 | NR | ||||
| Cai (USA) [13] | Retrospective Claims study (HealthCore Integrated Research database) | 374 | Higher dose than index biologic | UST (n = 119) | 6.9 | 2.7 |
| Cao (USA) [14] | Retrospective, observational study (Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental Coordination of Benefits databases) | 1000 | Change from 45 to 90 mg or 90 to 45 mg | UST (n = 1000) | 19.3 | 5.1 |
| Carrascosa (Spain) [7] | Observational, cross-sectional study (BIOBADADERM registry) | 637 | Higher or lower than EMA | ETA (n = 126) | 7.9 | 33.3 |
| UST (n = 230) | 10.4 | 30.9 | ||||
| INF (n = 51) | 13.7 | 29.4 | ||||
| ADA (n = 230) | 2.2 | 41.3 | ||||
| Carter (USA) [15] | Retrospective study (Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental Databases) | 7527 |
UST: higher than the patients’ initial dose ADA and ETA: average weekly dose in the maintenance period > 15% higher than the maintenance dose recommended on the product label |
ETA (n = 4011) | 30.9 | NR |
| UST (n = 583) | 18.2 | NR | ||||
| ADA (n = 2933) | 7.8 | NR | ||||
| Egeberg (USA) [16] | Cohort study (DERMBIO registry) | 2161 | Higher than EMA label | ETA (n = 579) | 39 (≤ 24 wks); 35.1 (25–52 wks) | NR |
| UST (n = 1055) | 20 (≤ 24 wks); 46.2 (25–52 wks) | NR | ||||
| INF (n = 333) | 22.7 (≤ 24 wks); 56.7 (25–52 wks) | NR | ||||
| ADA (n = 1332) | 3.5 (≤ 24 wks); 0.9 (25–52 wks) | NR | ||||
| SEC (n = 196) | 0 | NR | ||||
| Esposito (Italy) [9] | Retrospective, observational study (digital databases and/or medical records) | 350 | Shortening/lengthening of dosing interval and/or increasing/reduction of the drug per dose per single administration | ETA (n = 175) | 2.9 | 12.6 |
| UST (n = 40) | 7.5 | 0 | ||||
| INF (n = 49) | 24.5 | 22.4 | ||||
| ADA (n = 86) | 0 | 16.3 | ||||
| Esposito (Italy) [17] | Retrospective, observational study (medical records) | 115 | Dose in terms of frequency or administration variation | ETA (n = 106) | 10.4 | NR |
| INF (n = 9) | 33.3 | NR | ||||
| Feldman (USA) [18] | Retrospective study (MarketScan Commercial Encounters Database) | 4039 | Dose escalation or reduction was defined as the patient experiencing a dose increase or decrease of at least 25% following the titration window | ETA (n = 2452) | 41 | 48.7 |
| UST (n = 195) | 35.9 | 37.4 | ||||
| ADA (n = 1662) | 36.6 | 53.7 | ||||
| Feldman (USA) [19] | Retrospective cohort study (Truven Health MarketScan Commercial Encounters Database) | 3310 | 10% higher than indicated in the label for ≥ 180 days (consecutive/non-consecutive) over a 12-month period following the maintenance period | ETA (n = 1443) | 20 | NR |
| UST (n = 420) | 14.8 | NR | ||||
| ADA (n = 1447) | 2.6 | NR | ||||
| Gulliver (Canada) [20] | Observational, retrospective (Newfoundland and Labrador Centre for Health databases and The Newfoundland and Labrador Medical Care Plan (MCP) Fee-for-Service Physician Claims Database) | 248 | Increase dose/frequency | ETA (n = 47) | 25.5 | NR |
| UST (n = 54) | 16.7 | NR | ||||
| INF (n = 61) | 14.8 | NR | ||||
| ADA (n = 86) | 12.8 | NR | ||||
| Iskandar (UK) [8] | Observational cohort study (BADBIR registry) | 2980 | Change in average weekly dose | ETA (n = 996) | 11.4 | 5.2 |
| UST (n = 309) | 17.7 | 30.0 | ||||
| ADA (n = 1675) | 4.5 | 2.5 | ||||
| Lee (USA) [21] | Retrospective chart review (medical charts) | 34 | Any treatment regimen that differed from FDA-approved dosing | ETA (n = 34) | 29.4 | 11.8 |
| Luber (USA) [22] | Retrospective cohort study (medical records) | 93 | Increasing dose from 5 to 10 mg/kg or increasing infusion frequency from every 8 weeks to every 4 weeks | INF (n = 93) | 66.7 | NR |
| Romero-Jimenez (Spain) [23] | Observational, longitudinal and retrospective study (clinical histories) | 62 | Shortened or lengthened dosage interval compared with SPC | UST (n = 62) | 22.6 | 22.6 |
| Sanz-Gil (Spain) [24] | Retrospective, observational chart review (outpatient pharmacy unit database) | 74 | Lengthened dose interval, increased frequency of administration | ETA (n = 20) | 0 | 10 |
| UST (n = 33) | 15 | 9 | ||||
| ADA (n = 21) | 0 | 24 | ||||
| Schwensen (Denmark) [25] | Retrospective study (patient records and DERMBIO registry) | 69 | Patients initiated on 150 mg instead of recommended 300 mg | SEC (n = 69) | NR | 52.2 |
| Wilder (USA) [26] | Retrospective review (patient charts) | 119 | Increase in the dose of UST to 90 mg and/or administration more frequently than every 12 weeks | UST (n = 119) | 42 | NR |
| Wu (USA) [27] | Retrospective observational study (Truven Health Analytics MarketScan Databases) | 6732 | Increase of the dose between two consecutive prescription fills of at least 40 mg for ADA users and at least 45 mg for UST users | UST (n = 1795) | 19.5 (biologic naïve); 20.6 (biologic experienced) | NR |
| ADA (n = 4937) | 8.6 (biologic naïve); 11.0 (biologic experienced) | NR | ||||
| Zweegers (NL) [28] | Prospective study (BioCAPTURE registry) | 356 | Higher than EMA label | ETA (n = 245) | 55.1 | NR |
| UST (n = 90) | 17 | NR | ||||
| ADA (n = 178) | 31.5 | NR |
ADA adalimumab, EMA European Medicines Agency, ETA etanercept, FDA US Food and Drug Administration, INF infliximab, NR not reported, SEC secukinumab, SPC Summary of Product Characteristics, UST ustekinumab