438 Relevance of adalimumab serum concentration and anti-adalimumab antibodies in secondary loss of response in patients with juvenile idiopathic arthritis

Objective.Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response.Methods.S100A12 serum concentration was determined by ELISA in patients treated with MTX (n = 75) and anti-TNF (n = 88) at baseline and followup. Treatment response (≥ ACRpedi50 score), achievement of inactive disease, and improvement in Juvenile Arthritis Disease Activity Score (JADAS)-10 score were recorded.Results.Baseline S100A12 concentration was measured in patients treated with anti-TNF [etanercept n = 81, adalimumab n = 7; median 200, interquartile range (IQR) 133–440 ng/ml] and MTX (median 220, IQR 100–440 ng/ml). Of the patients in the anti-TNF therapy group, 74 (84%) were also receiving MTX. Responders to MTX (n = 57/75) and anti-TNF (n = 66/88) therapy had higher baseline S100A12 concentration compared to nonresponders: median 240 (IQR 125–615) ng/ml versus 150 (IQR 87–233) ng/ml, p = 0.021 for MTX, and median 308 (IQR 150–624) ng/ml versus 151 (IQR 83–201) ng/ml, p = 0.002, for anti-TNF therapy. Followup S100A12 could be measured in 44/75 MTX-treated patients (34/44 responders) and 39/88 anti-TNF-treated patients (26/39 responders). Responders had significantly reduced S100A12 concentration (MTX: p = 0.031, anti-TNF: p < 0.001) at followup versus baseline. Baseline serum S100A12 in both univariate and multivariate regression models for anti-TNF therapy and univariate analysis alone for MTX therapy was significantly associated with change in JADAS-10.Conclusion.Responders to MTX or anti-TNF treatment can be identified by higher pretreatment S100A12 serum concentration levels.

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Therapeutic Drug Monitoring Guides the Management of Crohn’s Patients with Secondary Loss of Response to Adalimumab

Inflammatory Bowel Diseases ◽

10.1093/ibd/izy044 ◽

2018 ◽

Vol 24 (7) ◽

pp. 1531-1538 ◽

Cited By ~ 16

Author(s):

Sophie Restellini ◽

Che-yung Chao ◽

Peter L Lakatos ◽

Achuthan Aruljothy ◽

Haya Aziz ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Therapeutic Drug ◽

Secondary Loss ◽

Loss Of Response

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P600 Vedolizumab dose optimisation: Findings from a Belgian registry

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.728 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S501-S502

Author(s):

E Louis ◽

V Muls ◽

P Bossuyt ◽

A Colard ◽

A Nakad ◽

...

Keyword(s):

Clinical Response ◽

Median Duration ◽

Real World ◽

Clinical Remission ◽

Outcome Data ◽

Real World Data ◽

Secondary Loss ◽

Loss Of Response ◽

Starting Point ◽

Dose Optimisation

Abstract Background Vedolizumab (VDZ) dose optimisation (DO), by interval shortening from 8-weekly (Q8W) to 4-weekly (Q4W) dosing, is used for patients with secondary loss of response. This report presents outcome data on patients receiving DO in real-world clinical practice in Belgium. Methods The Belgian VDZ Registry (ENcePP EUPAS6469) enrolled 202 VDZ-treated ulcerative colitis (UC) or Crohn’s disease (CD) adult patients (26% with no prior use of anti-TNF therapy) from 19 centres. The median length of VDZ therapy prior to enrolment was 11 months. Patients were followed-up every 6 months with the assessment of IBD features, use of biologics, and disease activity. Clinical remission was defined as Harvey–Bradshaw Index (HBI) <5 or partial Mayo Score (pMS) <2, and clinical response as a 2+ point improvement in pMS or a 3+ improvement in HBI. Results During a median follow-up of 19 months from enrolment, 57 (28%) patients (41 CD and 16 UC) received VDZ Q4W due to secondary loss of response. Q4W was mostly used in patients with CD or with prior anti-TNF therapy failure. The median starting point for Q4W dosing was 16 months after the start of VDZ (interquartile range (IQR) 8–27 months) and median duration of Q4W dosing was 4 months (IQR 2–8 months). After changing to Q4W dosing 44% achieved clinical remission, 3% clinical response, and 53% showed no improvement (Table 1). Among the 17 patients with clinical remission/response on Q4W dosing, 53% de-escalated back to Q8W, and continued with Q8W for a median duration of 12 months, 23.5% remained on Q4W with clinical remission, and 23.5% eventually stopped VDZ due to loss of response. A limitation of this study is that it did not systematically collect data on DO prior to recruitment, hence the proportion of patients receiving DO may be higher than reported here. Conclusion These real-world data show DO plays an important role in management of UC and CD. In this study, 28% of patients received DO following the secondary loss of response to Q8W therapy. Forty-seven per cent of patients receiving Q4W subsequently returned to clinical remission or had a clinical response, and half of these patients successfully returned to Q8W VDZ therapy. Controlled studies are warranted, ideally blinded, using more objective endpoint to reveal the true success rate of dose-optimisation.

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