Table 1. Characteristics of the studies.
| Author, Year of publication, Country | Patients | Biologic treatment | Comparative treatment | Perspective | Time horizon, Type of modelling | Source of effectiveness | Source of utility data, Instruments or valuation methods for utility measures | Discount rate |
|---|---|---|---|---|---|---|---|---|
| Crohn’s disease | ||||||||
| Ananthakrishnan et al. 2011, USA [39] | CD patients, who were in surgical remission after their first ileocecal resection | Upfront IFX or Tailored IFX | Antibiotic | Third-party payer | 1 year, Decision tree model | Meta-analysis systematic review, cohort studies | Utility values derived from study by Casellas et al [57], for surgery and after surgery by a panel of UK gastroenterologists, EQ-5D, utilities valued using UK tariffs | - |
| Ananthakrishnan et al. 2012, USA [40] | Moderate-to severe luminal CD, loss of response to two prior TNF inhibitors | NTZ | CTZ | Third-party payer | 1 year, Decision tree model | RCTs, multi-center report, cohort study | Utility values derived from study by Gregor et al [58], SG, utility scores classified by CDAI | - |
| Arseneau et al. 2001, USA [41] | Fistulizing CD | First-line IFX, second-line 6MP+MET or IFX episodic reinfusion or First-line 6MP+MET, second-line IFX episodic reinfusion | 6MP+MET | Third-party payer | 1 year, Markov model | Systematic review | Preference weights were directly elicited from CD patients and healthy individuals, SG | 3% for costs and benefits |
| Assasi et al. 2009, Canada [22] | Moderate-to severe CD (CDAI ≥ 200), refractory to conventional medical treatment | IFX 5 mg/kg induction and maintenance treatment or ADA induction treatment (160 mg at week 0, 80 mg at week 2) and maintenance treatment (40 mg) | Conventional medical treatment or ADA induction treatment (160 mg at week 0, 80 mg at week 2) and maintenance treatment (40 mg) | Third-party payer | 5 years, Markov model | Systematic review | Utility values derived from study by Gregor et al [58], SG | 5% for costs and QALYs |
| Blackhouse et al. 2012, Canada [42] | Refractory to conventional medical treatment (CDAI > 200) | IFX 5 mg/kg induction and maintenance treatment or ADA induction treatment (160 mg at week 0, 80 mg at week 2) and maintenance treatment (40 mg) | Conventional medical treatment or ADA induction treatment (160 mg at week 0, 80 mg at week 2) and maintenance treatment (40 mg) | Third-party payer | 5 years, Markov model | Systematic review | Utility values derived from study by Gregor et al [58], SG | 5% for costs and QALYs |
| Bodger et al. 2009, UK [43] | Moderate-to severe active CD, (CDAI > 220) | IFX 5 mg/kg + conventional medical treatment or ADA 80 mg at week 0, 40 mg at week 2, 40 mg for maintenance + conventional treatment | Conventional treatment | Payer, UK NHS | 60 years (lifetime), duration of treatment 1 or 2 years, Markov model | Systematic review | EQ-5D converted from CDAI (EQ-5D = 0.9168–0.0012 × CDAI, algorithm by Buxton et al [59]) | 3.5% for costs and QALYs |
| Clark et al. 2003, UK [44] | a, b) Severe active CD, c) Fistulizing CD | IFX 5 mg/kg single dose or IFX 5 mg/kg episodic re-treatment if lost response or IFX 5 mg/kg maintenance treatment | Placebo | Unclear | a) Lifetime, b) Unclear, probably 1 year, c) 1 year, a) Markov model, b,c) Type of modeling unclear | a, b) RCTs, c)RCT | a, b) Utility values derived from study by Gregor et al [58], SG, utility scores corresponding to the exact CDAI states, c) Combination of CDAI and PDAI score into utility using an unpublished formulae | 6% for costs and 1.5% for QALYs |
| Doherty et al. 2012, USA [45] | CD patients undergone intestinal resection | IFX 5 mg/kg induction and maintenance treatment | AZA / 6MP | Societal | 1 year, 5 years, Decision analysis model | Meta-analysis | Utility values derived from study by Gregor et al [58], SG, utility scores classified by CDAI | 3% |
| Dretzke et al. 2011, UK [21] | Moderate-to-severe CD, refractory to conventional medical treatment | IFX induction treatment or IFX maintenance treatment or ADA induction treatment or ADA maintenance treatment | Conventional medical treatment or IFX induction treatment or ADA induction treatment | Payer, UK NHS | 1 year, Markov model | Systematic review | Utility values derived from study by Gregor et al [58], assumptions for surgery, TTO, EQ-5D | 3.5% for costs and QALYs |
| Jaisson-Hot et al. 2004, France [46] | Moderate-to-severe active ileocolonic non fistulizing CD (CDAI 220–440), resistant to conventional medical treatment | IFX with retreatment when patients relapse/do not respond or IFX maintenance treatment | Surgery involving conventional medical treatment | Third-party payer | Lifetime, Markov model | RCT, expert opinion, cohort study | Utility values derived from study by Gregor et al [58], SG, utility scores classified by CDAI | 5% for costs and QALYs |
| Kaplan et al. 2007, USA [47] | CD patients, no response to 5 mg/kg of IFX | IFX dose escalation to 10 mg/kg | ADA initiation | Unclear | 1 year, Decision analysis model | RCTs, cohort study | Utility values derived from study by Gregor et al [58], SG, utility scores classified by CDAI | - |
| Lindsay et al. 2008, UK [48] | Active luminal non-fistulizing CD (CDAI 220–400) or Active fistulizing CD | IFX 5 mg/kg | Conventional medical treatment | Payer, UK NHS | 5 years, Markov model | RCTs, cohort study | Utility values derived from study by Casellas et al [57], for surgery and after surgery by a panel of UK gastroenterologists, EQ-5D, utilities valued using UK tariffs | 3.5% for costs and QALYs |
| Loftus et al. 2009, UK [49] | Moderate-to-severe CD | ADA | Conventional medical treatment | Payer, UK NHS | 1 year, Type of modeling unclear | RCTs | Utility values derived from study by Gregor et al [58], SG, utility scores classified by CDAI | 3.5% for costs and QALYs |
| Marchetti et al. 2013, Italy [50] | Newly diagnosed luminal moderate-to-severe CD patients | Top-down strategy: IFX 5 mg/kg+AZA à additional IFX 5 mg/kg+AZA à MPR+AZA | Step-up strategy: MPR à MPR+AZA à IFX+AZA | Third-party payer | 5 years, Markov model | RCT, cohort studies | EQ-5D and SF-6D converted from CDAI, SF-6D = 0.8129–0.00076 × CDAI, EQ-5D = 0.9168–0.0012 × CDAI, by Buxton et al | 3.5% for costs and QALYs |
| Marshall et al. 2002, Canada [19] | CD patients resistant to conventional medical treatment | IFX 5 mg/kg single dose, relapses treated with conventional treatment or IFX 5 mg/kg single dose, relapses treated with IFX 5 mg/kg single dose or IFX 5 mg/kg single dose with responding patients IFX 5 mg/kg maintenance treatment, relapses treated with conventional medical treatment | Conventional treatment or IFX 5 mg/kg single dose, relapses treated with conventional treatment or IFX 5 mg/kg single dose, relapses treated with IFX 5 mg/kg single dose | Third-party payer | 1 year, Markov model | RCTs, cohort study | Utility values derived from study by Gregor et al [58], SG, utility scores classified by CDAI | - |
| Saito et al. 2013, UK [51] | Biologic-naive CD patients refractory to conventional medical treatment (CDAI 220–450) | IFX 5 mg/kg+AZA | IFX 5 mg/kg | Payer, UK NHS | 1 year, Decision tree model | RCTs, observational study | Utility values derived from study by Gregor et al [58], expert opinion data for non-responding active disease, SG, utility scores classified by CDAI | - |
| Tang et al. 2012, USA [52] | Moderate-to-severe CD (CDAI 220–450), refractory to conventional medical treatment and naïve to biologics | ADA or CTZ or NTZ | IFX | Third-party payer | 1 year, Decision analytic model | RCTs | Utility values derived from study by Gregor et al [58], SG, utility scores classified by CDAI | - |
| Yu et al. 2009, USA [56] | Active moderate-to-severe CD, candidate for anti-TNF maintenance treatment | ADA (40 mg every other week) maintenance treatment | IFX 5 mg/kg maintenance treatment | Third-party payer | 1 year, Type of modeling unclear | RCTs | Utility values derived from study by Gregor et al [58], SG, utility scores classified by CDAI | - |
| Ulcerative colitis | ||||||||
| Assasi et al. 2009, Canada [22] | Moderate-to-severe UC, refractory to conventional medical treatment | IFX 5 mg/kg followed by switching to ADA 160 mg when relapse or IFX 5 mg/kg followed by IFX 10 mg/kg dose escalation when relapse | Conventional medical treatment or IFX 5 mg/kg followed by switching to ADA 160 mg when relapse | Third-party payer | 5 years, Markov model | Systematic literature review | TTO, Utility weights elicited from UC patients | 5% for costs and QALYs |
| Bryan et al. 2008, UK [37] | Acute exacerbation of UC that require hospitalization, inadequate response to conventional medical treatment | IFX 5 mg/kg+IV CST | Placebo or CYC or Surgery | Payer, UK NHS | 1 year, Decision analytic model | RCTs | EQ-5D, Utility weights derived from UC patients | 3.5% for costs and QALYs |
| Chaudhary et al. 2013, Netherlands [36] | Severely active UC, hospitalized with an acute exacerbation of UC, refractory to IV CST | IFX 5 mg/kg | IV CYC or Surgery | Third-party payer | 1 year, Decision analytic model, beyond the first year a Markov model | RCTs | EQ-5D, valued using UK tariffs, TTO for post-surgery complications, Utility scores classified by SCAI, Utility weights derived from UC patients | 4% for costs, 1.5% for QALYs |
| Hyde et al. 2007, UK [38] | Moderate-to-severe active UC, an inadequate response to conventional medical treatment | IFX 5 mg/kg | Conventional treatment | Payer, UK NHS | 10 years, Markov model | RCTs | EQ-5D, Utility weights derived from UC patients | 3.5% for costs and QALYs |
| Punekar et al. 2010, UK [35] | Severely active UC, hospitalized with an acute exacerbation of UC, refractory to IV CST | IFX 5 mg/kg + IV CST | IV CST or CYC+IV CST or Surgery | Payer, UK NHS | 1 year, Decision analytic model, beyond the first year a Markov model | A network meta-analysis | EQ-5D, valued using UK tariffs, TTO for post-surgery complications, Utility scores classified by SCAI, Utility weights derived from UC patients | 3.5% for costs and QALYs |
| Tsai et al. 2008, UK [53] | Moderate-to-severe UC | Scheduled maintenance treatment with IFX 5 mg/kg | Conventional medical treatment | Payer, UK NHS | 10 years, Markov model | RCTs | EQ-5D, valued using UK tariffs, TTO for post-surgery complications, Utility scores classified by SCAI, Utility weights derived from UC patients | 3.5% for costs and QALYs |
| Ung et al. 2014, Canada [54] | Moderate or moderately severe UC, CST-dependent and refractory to thiopurine | IFX 5 mg/kg | Conventional medical treatment | Third-party payer | 10 years, Markov model | RCTs, real life rates | TTO, VAS, Utility weights derived from UC patients | 5% for costs and QALYs |
| Xie et al. 2009, Canada [55] | Moderate-to-severe UC, refractory to conventional medical treatment | IFX 5 mg/kg followed by IFX 10 mg/kg dose escalation when relapse or IFX 5 mg/kg followed by switching to ADA 160 mg when relapse | Conventional medical treatment | Third-party payer | 5 years, Markov model | Fixed-effect meta-analysis | TTO, Utility weights derived from UC patients | 5% for costs and QALYs |
→, Transition because of the clinical worsening in the earlier state; 6MP, Mercaptopurine; ADA, Adalimumab; AZA, Azathioprine; CD, Crohn’s disease; CDAI, Crohn’s disease activity index; CST, Corticosteroid; CTZ, Certolizumab pegol; CYC, Cyclosporine; EQ-5D, European Quality of Life Instrument 5 D; IBDQ-36, Inflammatory Bowel Disease Questionnaire 36; IFX, Infliximab; IV, Intravenous; MET, Metronidazole; MPR, Methylprednisolone; NTZ, Natalizumab; PDAI, Pouchitis Activity Index; QALY, Quality-Adjusted Life Year; RCT, Randomized controlled trial; SCAI, Simple Clinical Colitis Activity Index; SF-6D, Short Form-6 dimension; SG, Standard gamble; TNF, Tumor necrosis factor; TTO, Time Trade-Off; UC, Ulcerative colitis; UK NHS, National Health Service (England); VAS, Visual Analog Scale.