CK, BH-B JEG, GlM, VN-C, JI and AvT conducted the study. Funding: This project was funded by EULAR (project number CLI114). Disclaimer: The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health and Care Study or the Division of Health and Sociable Care. Competing interests: AvT received unrestricted research grants from Pfizer, Abbvie, Novartis, UCB and Biogen and consultancy charges from AG-024322 Novartis; Abdominal received give/study support and charges for consultancies or like a speaker from Abbvie, Amgen, Pfizer, Novartis, BMS, Nordic, Sanofi, Sandoz, Lilly, UCB and Roche; MJ received travel expenses from Abbvie and speaker charges from Grifols in the last 5 years; DM acted like a specialist and offered lectures on behalf of his institution for Pfizer, Novartis and Grifols and was invited to attend an international congress by Janssen-Cilag; his institution received grants for research from your non-governmental organisation Lions Golf club Trips Val de France; VN-C received study grants/honoraria from AbbVie, Janssen, Lilly, Moonlake, Novartis, Pfizer and UCB; JDI received give income from Pfizer, GSK and Janssen and consultancy/speaker charges/sponsorship from Abbvie, AG-024322 Eli Lily, Gilead, Roche and UCB. Provenance and peer review: Not commissioned; externally peer reviewed. Supplemental material: This content has been supplied by the author(s). body weight, methotrexate comedication and disease activity. The recognition of a target range was hampered by study variability, primarily disease activity steps and study type. Evidence was inconsistent for multiple medical situations in which TDM is currently applied. However, for some particular scenarios, including prediction of long term treatment response, non-response to treatment, tapering and hypersensitivity reactions, strong evidence was found. There is currently no evidence for routine use of proactive TDM, in part because published cost-effectiveness analyses do not incorporate the current scenery of biopharmaceutical costs and utilization. This SLR yields evidence in favour of TDM of biopharmaceuticals in some clinical scenarios, but evidence is insufficient to support implementation of routine use of TDM. Six studies addressed this situation, one in axSpA and five in RA.7 52 66 125C127 In a small study in axSpA, numerically more individuals with suboptimal golimumab blood concentrations ( 0.7?g/mL) before tapering had a disease flare after tapering.127 In RA, a modelling study with tocilizumab suggested no added good thing about TDM-guided tapering, with flare rates comparable to empirical dose tapering.125 Inside a post hoc analysis of an RCT AG-024322 in which individuals with RA were randomised to discontinue adalimumab, trough concentrations did not predict individuals that flared after discontinuation.126 In another RCT, in which individuals with RA with high adalimumab blood concentrations were randomised to dose interval prolongation or continuation of treatment every 2 weeks, interval prolongation did not increase flare rate.7 In another study combining data from post hoc analyses of an RCT and an observational study, no predictive value of adalimumab, etanercept or infliximab blood AG-024322 concentrations for successful discontinuation or dose reduction could be demonstrated, except for a subset of individuals with high adalimumab blood concentrations (cut-off 7.8?g/mL) and a small inverse association between lower etanercept concentration (cut-off 2.6?g/mL) and successful dose de-escalation.52 In a further observational study, individuals with RA who remained in remission or in a state of low disease activity after dose halving of adalimumab had significantly higher adalimumab blood concentrations compared with those who flared, having a baseline cut-off of 6.4?g/mL for persistent remission and 1.9?g/mL for persistent low disease activity.66 In four observational studies and one post hoc study of an RCT, TNF-inhibitor blood concentration measurement did not predict successful dose escalation in cases of clinical non-response in individuals with RA or SpA.79 128C131 Biopharmaceutical blood concentrations were similar prior to dose escalation in individuals who did or did not respond to dose escalation. Results from eight studies on subsequent response to treatment after switching from one to another biopharmaceutical in case of low blood concentrations or presence of ADAb were conflicting.132C139 In three observational RA studies, ADAb at time of infliximab failure did not forecast success of subsequent adalimumab or etanercept treatment.137C139 However, two other observational studies in RA and SpA suggested that ADAb expected successful switching from a first to Rabbit Polyclonal to EDNRA a second TNF inhibitor.135 136 In two studies, both biopharmaceutical blood concentrations and ADAb were measured; these studies showed conflicting results. 132 134 In a study including adalimumab non-responders switching to etanercept, numerically more individuals with very low adalimumab levels ( 0.5?g/mL) had EULAR moderate to good reactions 52 weeks after switching.133 A prospective study measured biopharmaceutical blood concentrations (rituximab, infliximab and etanercept) in the 1st sign of a flare (ie, increase in CRP or ESR or in disease activity).140 Patients with detectable blood concentrations had reduce.
CK, BH-B JEG, GlM, VN-C, JI and AvT conducted the study
