Association Between Infliximab Trough Levels and the Occurrence of Paradoxical Manifestations in Patients with Inflammatory Bowel Disease: a Case-Control Study.
OBJECTIVE
Anti-tumour necrosis factor [TNF] agents have dramatically improved the prognosis of inflammatory bowel disease [IBD]. However, despite their good safety profile, use of these agents may lead to paradoxical manifestations involving skin or joints. Pathogenesis of such side effects is poorly understood and may involve anti-TNF pharmacokinetics. The aim of the present study was to look for an association between infliximab trough levels [ITL] and cutaneous [CPM] or rheumatological [RPM] paradoxical manifestations.


METHODS
IBD patients receiving infliximab as maintenance therapy were included in a cross-sectional prospective monocentre study. At inclusion, patients had an ITL measurement [LISA-TRACKER®, Biomedical Diagnostics BMD] and were assessed for paradoxical manifestations: a CPM was defined by new onset or exacerbation of pre-existing psoriasis lesions during IFX therapy, and an RPM by new onset of severe poly-arthralgia during IFX therapy.


RESULTS
Among the 121 patients included [69 female; median age: 38.9 years; 92 with Crohn's disease], 7% had CPM and 8% RPM. Median ITL values were 5.87 [range: 0.52-19.53] µg/ml in patients with CPM and 1.90 [0.00-13.5] µg/ml in those with RPM, as compared respectively with 5.12 [0.00-49.12] µg/ml in patients without CPM [p = 0.56] and 5.57 [0.00-49.12] µg/ml in those without RPM [p = 0.058]. No prognostic factor was associated with CPM. The single factor associated with RPM was elevated antinuclear antibodies.


CONCLUSIONS
ITL were not elevated in IBD patients developing cutaneous or rheumatological paradoxical manifestations when receiving IFX as maintenance therapy. As suggested by the high level of antinuclear antibodies, RPM could be related to an induced autoimmune disorder.
Service d'Hépato-gastroentérologie, CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac, France.
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Coutzac
Service d'Hépato-gastroentérologie, CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac, France.
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Chapuis
Service d'Hépato-gastroentérologie, CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac, France.
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Poullenot
Service d'Hépato-gastroentérologie, CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac, France.
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Chabrun
Service d'Hépato-gastroentérologie, CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac, France.
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Capdepont
Laboratoire d'immunologie, CHU de Bordeaux, Hôpital Pellegrin, Bordeaux, France.
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Blanco
Service d'Hépato-gastroentérologie, CHU de Bordeaux, Hôpital Haut-Lévêque, Pessac, France david.laharie@chu-bordeaux.fr.
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Laharie
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000209:etiology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005765:Gastrointestinal Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000069285:Infliximab / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016015:Logistic Models; D060046:Maintenance Chemotherapy / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011565:Psoriasis / Q000175:diagnosis / Q000209:etiology*; D055815:Young Adult
D005765:Gastrointestinal Agents; D000069285:Infliximab
Crohn’s disease; Infliximab; inflammatory bowel disease; infliximab trough level; paradoxical manifestations; psoriasis; ulcerative colitis