Tight control for Crohn's disease with adalimumab-based treatment is cost-effective: an economic assessment of the CALM trial

Abstract

Objective: To evaluate the cost-effectiveness of an inflammatory biomarker and clinical symptom directed tight control strategy (TC) compared with symptom-based clinical management (CM) in patients with Crohn's disease (CD) naïve to immunosuppressants and biologics using a UK public payer perspective.

Design: A regression model estimated weekly CD Activity Index (CDAI)-based transition matrices (remission: CDAI <150, moderate: CDAI ≥150 to <300, severe: CDAI ≥300 to <450, very severe: CDAI ≥450) based on the Effect of Tight Control Management on Crohn's Disease (CALM) trial. A regression predicted hospitalisations. Health utilities and costs were applied to health states. Work productivity was monetised and included in sensitivity analyses. Remission rate, CD-related hospitalisations, adalimumab injections, other direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated.

Results: Over 48 weeks, TC was associated with a higher clinical remission (CDAI <150) rate (58.2% vs 46.8%), fewer CD-related hospitalisations (0.124 vs 0.297 events per patient) and more injections of adalimumab (40 mg sc) (mean 31.0 vs 24.7) than CM. TC was associated with 0.032 higher QALYs and £593 higher total medical costs. The ICER was £18 656 per QALY. The ICER was cost-effective in 57.9% of simulations. TC became dominant, meaning less costly but more effective, when work productivity was included.

Conclusion: A TC strategy as used in the CALM trial is cost-effective compared with CM. Incorporating costs related to work productivity increases the economic value of TC. Cross-national inferences from this analysis should be made with caution given differences in healthcare systems.

Trial registration number: NCT01235689; Results.

Keywords: Crohn’s disease; TNF-alpha; cost-effectiveness; economic evaluation.

Conflict of interest statement

Competing interests: RP has received consultant and/or lecture fees from AbbVie, Amgen, AstraZeneca, Axcan Pharma (now Aptalis), Biogen Idec, Bristol-Myers Squibb, Centocor, ChemoCentryx, Eisai Medical Research Inc, Elan Pharmaceuticals, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck Sharp & Dohme Corp, Millennium Pharmaceuticals Inc (now Takeda), Ocera Therapeutics Inc, Otsuka America Pharmaceutical, Pfizer, Shire Pharmaceuticals, Prometheus Laboratories, Schering-Plough Corporation, Synta Pharmaceuticals Corp, Teva, UCB Pharma and Warner Chilcott. J-FC has been a consultant or advisory board member for AbbVie, Amgen, Boehringer-Ingelheim, Celgene Corporation, Celltrion, Enterome, Ferring, Genentech, Janssen and Janssen, Medimmune, Merck & Co, Pfizer, Protagonist, Second Genome, Seres, Shire, Takeda, Theradiag, speaker for AbbVie, Ferring, speaker’s bureau for Amgen, stock options of Intestinal Biotech Development, Genefit. Research Grants: AbbVie, Takeda, Janssen and Janssen. SPLT has been a consultant or advisory board member for AbbVie, Ajinomoto, Amgen, Almirall, Asahi, Atlantic, Bioclinica, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Calcico, Celgene, Chemocentryx, Cosmo, Covance, Enterome, Falk, Ferring, Genentech, Gilead, Giuliani SpA, GlaxoSmithKline, Glenmark, Grunenthal, Immunocore, Immunometabolism, Istesso, Janssen, Lexicon, Lilly, Medarex, Merck, MSD, Napp, Neovacs, NovoNordisk, Novartis, NPS Pharmaceuticals, Ocera, Otsuka, Pfizer, PharmOlam, Phillips, Proximagen, Qunitiles, Receptos, Robarts, Roche, Sandoz, Shire, Sigmoid Pharma, Takeda, Theravance, TiGenix, Topivert, UCB, Warner Chillcott, Vertex, VHsquared, Vifor and Zeria; speaker for AbbVie, Amgen, Biogen, Ferring, Sandoz, Takeda, Zeria; and received research grants from AbbVie, Buhlmann, Lilly, MediAdd, UCB, Vifor and the Norman Collisson Foundation. PB has received educational grants from AbbVie, Janssens; speaker fees from AbbVie, Takeda and MSD; and advisory board fees from Abbvie, Hospira, Janssen, MSD, Mundipharma, Roche, Pfizer and Dr Falk Benelux. FB has received research grants from Abbvie, Chiesi, Ipsen, MSD, Roche, speakers and consultancy fees from Abbvie, Falk, Ferring, Janssen, Mundipharma, MSD, Pfizer, Takeda, and Vifor. TV has served as advisory member for Hospira, Pfizer and Takeda, has received lecture fees from Takeda. GN has served as a consultant/advisory board member/speaker for AbbVie, MSD, Takeda, Ferring, Vifor, Merck, Janssen and Pfizer. AA has served as a consultant or advisory member for AbbVie, Allergan, Amgen, Biogen, Celgene, Celltrion, Ferring, Hospira, Janssen, Lilly, MSD, Mundipharma, Pfizer, Samsung Bioepis, Sofar and Takeda, has received lecture fees from AbbVie, AstraZeneca, Chiesi, Ferring, Hospira, Medtronic, MSD, Mitsubishi Tanabe, Mundipharma, Nikkiso, Otsuka, Pfizer, Takeda, Tigenix and Zambon, has received research funding from MSD and Takeda. WR has served as a speaker for Abbott Laboratories, Abbvie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, Yakult; as a consultant for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, Elan, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, Mallinckrodt, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough, Second Genome, Setpointmedical, Sigmoid, Takeda, Therakos, Tigenix, UCB, Vifor, Zyngenia and 4SC; as an advisory board member for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zyngenia, and 4SC; and has received research funding from Abbott Laboratories, Abbvie, Aesca, Centocor, Falk Pharma GmbH, Immundiagnsotik, and MSD. SJ and MB are employees of Medicus Economics LLC which was paid fees by AbbVie to conduct the research in the manuscript. EN, JP and W-JL are AbbVie employees and may own AbbVie stock and/or options. GRD’H is a consultant for AbbVie, ActoGeniX NV, AGI Therapeutics, Inc, Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys, Inc, Atlantic Healthcare Limited, Aptalis, BioBalance Corporation, Boehringer Ingelheim, Inc, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine PharmaSciences, Eagle Pharmaceuticals, Eisai Medical Research Inc, Elan Pharmaceuticals, enGene, Inc, Eli Lilly, EnteroMedics, Exagen Diagnostics, Inc, Ferring Pharmaceuticals, Flexion Therapeutics, Inc, Funxional Therapeutics Limited, Genzyme Corporation, Genentech, Gilead Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Ironwood Pharmaceuticals, Janssen, KaloBios Pharmaceuticals, Inc, Lexicon Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals, Merck Research Laboratories, Merck Serono, Merck & Co., Millennium, Nisshin Kyorin Pharmaceuticals Co, Ltd, Novo Nordisk A/S, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics, Inc, PDL BioPharma, Pfizer, Procter & Gamble, Prometheus Laboratories, ProtAb Limited, PurGenesis Technologies, Inc, Receptos, Relypsa, Inc, Salient Pharmaceuticals, Salix Pharmaceuticals, Inc, Santarus, Shire Pharmaceuticals, Sigmoid Pharma Limited, Sirtris Pharmaceuticals, Inc (a GSK company), SLA Pharma (UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Limited (VBL) and Warner Chilcott UK Limited; has received speaker fees from AbbVie, Bristol-Myers Squibb and Janssen; and has received financial support for research from AbbVie, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Millennium, Novartis, Pfizer, Procter & Gamble Pharmaceuticals, Shire Pharmaceuticals and UCB Pharma.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Observed and predicted cumulative incidence of CD-related hospitalisations. Cumulative incidence of CD-related hospitalisation based on observed cumulative hospitalisations in CALM (A) and modelled cumulative hospitalisations (B) based on regression in online supplementary table S3. CALM, Effect of Tight Control Management on Crohn’s Disease trial; CD, Crohn’s disease; ITT, intent-to-treat.

Figure 2

One-way sensitivity analysis of tight control versus clinical management base-case analysis. Values in base case and sensitivity analyses appear in table 1. CALM, Effect of Tight Control Management on Crohn’s Disease trial CDAI, Crohn’s disease Activity Index; ICER,  incremental cost-effectiveness ratio;  NHS, National Health Service; SA, sensitivity analysis.

Figure 3

Cost-effectiveness acceptability curves (CEAC) of tight control versus clinical management excluding (base case) and including absenteeism due to Crohn’s disease (CD) effects. To illustrate the uncertainty surrounding incremental cost-effectiveness ratio (ICER) estimates, the CEACs depict the probability that the tight control   strategy (TC) strategy is preferred to the clinical management (CM) strategy across a range of cost-effectiveness ratios. Results are depicted for the analysis excluding absenteeism (hashed lines) and including absenteeism (solid grey line). Results are based on the probabilistic sensitivity analysis, which included 1000 second-order Monte Caro simulations in which model variables were simultaneously varied. The solid black vertical line indicates the £30 000 per quality-adjusted life-years (QALY) willingness-to-pay threshold commonly used as a benchmark in the UK. 57.9% of simulations were at the threshold when excluding absenteeism, indicating that TC was likely better value considering costs and QALYs than CM; 81.8% were below the threshold when including absenteeism, indicating TC was more probably good value versus CM in that scenario.