Therapeutic drug monitoring guides the management of patients with chronic non-infectious uveitis treated with adalimumab: a retrospective study

Séjournet, Lucas; Kerever, Sébastien; Mathis, Thibaud; Kodjikian, Laurent; Jamilloux, Yvan; Sève, P.

doi:10.1136/bjophthalmol-2021-319072

Cited by 10 publications

(9 citation statements)

References 23 publications

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“…Assuming this is the case, it would be of great importance to monitor ADAbs levels throughout treatment to differentiate between transient and permanent antibody positivity, since only the latter is associated with subtherapeutic drug levels and with a higher risk of treatment failure. Subsequent studies have confirmed the relationship between a worse clinical response with lower trough ADA levels, which in turn are frequently found in patients with ADAbs [ 17 , 61 , 70 , 92 ]. Despite most studies in NIU having shown a protective effect of immunomodulatory therapy against the development of immunogenicity [ 17 , 61 , 70 ] in accordance with previous reports in other pathologies, Cordero-Coma et al [ 18 ] did not observe such an effect.…”

Section: Therapeutic Drug Monitoring Of Anti-tnfα In Niumentioning

confidence: 85%

“…Significantly higher trough ADA levels have been consistently reported in patients with NIU who responded to treatment compared to those non-responders. In addition, ADA trough levels have shown an inverse correlation with anti-ADA antibody levels [ 17 , 18 , 61 , 70 , 92 ]. Consequently, the presence of anti-ADA antibodies has been associated with treatment failure as assessed by a worse uveitis outcome and failure to achieve remission.…”

Section: Therapeutic Drug Monitoring Of Anti-tnfα In Niumentioning

confidence: 99%

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Perspectives of Therapeutic Drug Monitoring of Biological Agents in Non-Infectious Uveitis Treatment: A Review

et al. 2023

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Biological drugs, especially those targeting anti-tumour necrosis factor α (TNFα) molecule, have revolutionized the treatment of patients with non-infectious uveitis (NIU), a sight-threatening condition characterized by ocular inflammation that can lead to severe vision threatening and blindness. Adalimumab (ADA) and infliximab (IFX), the most widely used anti-TNFα drugs, have led to greater clinical benefits, but a significant fraction of patients with NIU do not respond to these drugs. The therapeutic outcome is closely related to systemic drug levels, which are influenced by several factors such as immunogenicity, concomitant treatment with immunomodulators, and genetic factors. Therapeutic drug monitoring (TDM) of drug and anti-drug antibody (ADAbs) levels is emerging as a resource to optimise biologic therapy by personalising treatment to bring and maintain drug concentration within the therapeutic range, especially in those patients where a clinical response is less than expected. Furthermore, some studies have described different genetic polymorphisms that may act as predictors of response to treatment with anti-TNFα agents in immune-mediated diseases and could be useful in personalising biologic treatment selection. This review is a compilation of the published evidence in NIU and in other immune-mediated diseases that support the usefulness of TDM and pharmacogenetics as a tool to guide clinicians’ treatment decisions leading to better clinical outcomes. In addition, findings from preclinical and clinical studies, assessing the safety and efficacy of intravitreal administration of anti-TNFα agents in NIU are discussed.

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Section: Therapeutic Drug Monitoring Of Anti-tnfα In Niumentioning

confidence: 85%

Section: Therapeutic Drug Monitoring Of Anti-tnfα In Niumentioning

confidence: 99%

Perspectives of Therapeutic Drug Monitoring of Biological Agents in Non-Infectious Uveitis Treatment: A Review

et al. 2023

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“…There are no established guidelines for the role of therapeutic drug monitoring (TDM) in patients receiving TNFis for NIU, although several studies showed that it may be beneficial. Sejournet et al, in their study on TDM in patients with chronic NIU, reported an ADA frequency of 13.6% among patients treated with adalimumab. Their results also showed that ADA formation and low drug levels together with clinical evidence of therapy failure were associated with increased adalimumab dose frequency in 13 of 31 patients (42%), an increased dose in 1 of 31 patients (3.2%), and intraclass or interclass switching in 10 of 31 patients (32%), suggesting that TDM may be useful in determining the need for treatment.…”

Section: Discussionmentioning

confidence: 99%

Antidrug Antibodies to Tumor Necrosis Factor α Inhibitors in Patients With Noninfectious Uveitis

et al. 2023

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ImportanceTumor necrosis factor inhibitors (TNFis) can induce antidrug antibody (ADA) formation and loss of therapeutic response. However, the utility of ADA testing and the association between ADAs and treatment response in patients with noninfectious uveitis (NIU) is not well understood.ObjectiveTo assess the frequency of ADAs and their association with drug levels and clinical response in patients with NIU treated with adalimumab or infliximab.Design, Setting, and ParticipantsThis retrospective cross-sectional study included patients diagnosed with NIU who received adalimumab or infliximab and underwent testing for serum drug level and ADAs at the National Eye Institute from September 2017 to July 2021.ExposuresSerum drug level testing with reflex testing for ADA levels was performed.Main Outcomes and MeasuresThe main outcome was the association between drug levels and ADAs, clinical response, and concurrent antimetabolite use in patients treated with TNFis for NIU.ResultsOf 54 patients included in the study, 42 received adalimumab (mean [SD] age, 43.6 [19.6] years; 25 [59.5%] female) and 12 received infliximab (mean [SD] age, 42.7 [20.4] years; 7 [58.3%] male). In the adalimumab group, mean (SD) drug level was 9.72 (6.82) μg/mL, mean (SD) ADA level was 84.2 (172.9) arbitrary units/mL, and ADA frequency was 35.7% (15 of 42 patients). Mean drug level was lower in those with ADAs compared with those without ADAs (mean [SD], 2.8 [2.6] μg/mL vs 13.6 [5.2] μg/mL; difference: 10.8 μg/mL; 95% CI, 8.3-13.2 μg/mL; P &lt; .001). There was a higher mean drug level with concurrent antimetabolite use compared with monotherapy (mean [SD], 11.0 [7.3] μg/mL vs 6.8 [4.5] μg/mL; difference: –4.2 μg/mL; 95% CI, –8.7 to 0.2 μg/mL; P = .06). Multivariable modeling showed that a 1−arbitrary unit increase in ADAs was associated with a –0.02 μg/mL (95% CI, –0.01 to –0.34 μg/mL) difference in mean drug level (P &lt; .001). Favorable clinical response was associated with a threshold drug level above 2.7 μg/mL or an antibody level below 15.2 μg/mL. The mean (SD) drug level in the infliximab group was 27.02 (18.15) μg/mL, and no ADAs were detected.Conclusions and RelevanceIn this study, 35.7% of adalimumab-treated patients with NIU had ADAs. The presence of ADAs was associated with lower drug levels, and higher ADA levels were associated with increased risk of TNFi treatment failure. Although limited by the retrospective design, our results suggest that therapeutic drug monitoring may be considered among patients experiencing therapy failure to help exclude ADAs as a potential cause of treatment failure.

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“…Overall, patients with ADA had a lower MDL, a finding that has been confirmed in other retrospective studies of NIU. 5 In a multivariate analysis, a 1 AU/mL increase in ADA level was associated with a 0.024 μg/mL decrease in drug concentration (P < .001). An adalimumab drug level greater than 3.3 μg/mL showed good sensitivity and low specificity with an area under the curve of 0.67 for the prediction of complete response.…”

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confidence: 89%

“…The mean drug level (MDL) and mean antibody level (MAL) were 9.72 μg/mL and 84.2 arbitrary units (AU)/mL, respectively. Overall, patients with ADA had a lower MDL, a finding that has been confirmed in other retrospective studies of NIU . In a multivariate analysis, a 1 AU/mL increase in ADA level was associated with a 0.024 μg/mL decrease in drug concentration ( P < .001).…”

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confidence: 95%

Therapeutic Drug Monitoring in Noninfectious Uveitis

Shantha

Acharya

2023

JAMA Ophthalmol

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Therapeutic drug monitoring guides the management of patients with chronic non-infectious uveitis treated with adalimumab: a retrospective study

Cited by 10 publications

References 23 publications

Perspectives of Therapeutic Drug Monitoring of Biological Agents in Non-Infectious Uveitis Treatment: A Review

Perspectives of Therapeutic Drug Monitoring of Biological Agents in Non-Infectious Uveitis Treatment: A Review

Antidrug Antibodies to Tumor Necrosis Factor α Inhibitors in Patients With Noninfectious Uveitis

Therapeutic Drug Monitoring in Noninfectious Uveitis

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