Therapeutic monitoring of TNF-alpha inhibitors in rheumatoid arthritis

and the full-text publication): • the mean drug administration interval was longer (p<0.001) • the mean weekly dose was lower (approximately 20% reduction; p<0.001). 4.16 Everyone had stable clinical activity in both periods. In people with rheumatoid arthritis, the mean (± standard deviation [SD]) DAS28 was 2.31±0.52 after introducing therapeutic monitoring of TNF-alpha inhibitors compared with 2.51±0.85 before (p=0.061). In the full-text publication the mean DAS28 was 2.37±0.50 and 2.28±0.47, respectively (p=0.2). Additional study by l'Ami et al. (2017) 4.17 The study was an open-label, randomised, parallel-group, non-inferiority trial done in the Netherlands. It assessed clinical outcomes in people with rheumatoid arthritis with high serum adalimumab concentrations (above 8 mg/ litre) who had dose-interval prolongation, compared with people who continued standard dosing. 4.18 The trial considered people with rheumatoid arthritis who had treatment for at least 28 weeks and had no indication for adjustment of adalimumab treatment, discontinuation or a scheduled surgery in the next 6 months. A total of 55 people were randomised and 54 included for analyses. 4.19 The mean DAS28 after 28 weeks decreased by 0.14 (SD 0.61) in the interval prolongation group and increased by 0.30 (SD 0.52) in the continuation group. The difference in the mean change in DAS28 was 0.44 (95% CI 0.12 to 0.76; p=0.01) in favour of the prolongation group. 4.20 The authors concluded that the frequency of adalimumab dosing can be safely extended without loss of disease control. However, because of the small sample size and comparable median adalimumab doses at week 28 in both groups, the EAG did not include this study in the economic assessment. Therapeutic monitoring of TNF-alpha inhibitors in rheumatoid arthritis (DG36) © NICE 2020. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-andconditions#notice-of-rights). Page 16 of 36 Cost effectiveness Systematic review of cost-effectiveness evidence 4.21 The EAG identified 5 studies investigating the cost effectiveness of ELISA tests used to measure drug levels and antidrug antibodies for monitoring response to TNF-alpha inhibitors. There were 3 studies that were model-based economic evaluations (cost-effectiveness models) and 2 were observational (PascualSalcedo et al. 2013 reported costs and Arango et al. 2017 reported costs and quality-adjusted life years [QALYs]). 4.22 In INGEBIO (see sections 4.6 to 4.11 for study details), the mean QALYs during the 18-month follow-up period were 1.076 in the control (standard care) group and 1.145 in the intervention group (therapeutic monitoring of TNF-alpha inhibitors). This was a gain of 0.069 QALYs compared with control (Arango et al. 2017). The average per patient-year costs of adalimumab were €10,665 in the control group and €9,856 in the intervention group. This was a cost saving of €808 (8% of cost). Other healthcare costs were not reported. Data in the full study report (commercial in confidence) were generally in line with the findings in the conference abstract. 4.23 In the observational study by Pascual-Salcedo et al. (2013; see sections 4.12 to 4.16 for study details), introducing therapeutic monitoring of TNF-alpha inhibitors resulted in lower monthly acquisition costs of TNF-alpha inhibitors, compared with the monthly costs of the drugs before monitoring. The monthly cost saving was €92 per person on infliximab (assuming a mean weight of 70 kg), €324 per person on adalimumab, and €257 per person on etanercept. In the fulltext publication the monthly cost saving was €143, €215, and €136 per person, respectively (Pascual-Salcedo et al. 2015). 4.24 Krieckaert et al. (2015) considered the cost effectiveness of a personalised treatment algorithm in people with rheumatoid arthritis taking adalimumab in the Netherlands. This was based on clinical response and drug levels (in-house ELISA tests, Sanquin) at 6 months of treatment, compared with standard care. The study population included all people who had treatment for 6 months, regardless of disease response. For 272 people starting adalimumab treatment over the period of 3 years, a test-based treatment strategy would: Therapeutic monitoring of TNF-alpha inhibitors in rheumatoid arthritis (DG36) © NICE 2020. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-andconditions#notice-of-rights). Page 17 of 36