Adalimumab for Treatment of Noninfectious Uveitis: Immunogenicity and Clinical Relevance of Measuring Serum Drug Levels and Antidrug Antibodies.
To evaluate the rate of immunogenicity induced by adalimumab and its relationship with drug serum levels and clinical responses in patients with noninfectious uveitis.



Prospective observational study.



Consecutive patients from 1 referral center who initiated treatment with adalimumab for active noninfectious uveitis resistant to conventional therapy.



All patients received 40 mg adalimumab every other week. Patients were evaluated clinically and immunologically before and after 4, 8, and 24 weeks of treatment.



Clinical evaluation included assessment of changes in visual acuity, degree of inflammation in the anterior chamber and vitreous cavity, central macular thickness, and retinal angiographic leakage. Immunologic evaluation included assessment of serum trough adalimumab and antibodies against adalimumab (AAA) levels and class II HLA typing.



Twenty-five patients were enrolled. Overall, 18 of 25 patients (72%) showed a favorable clinical response to adalimumab therapy. Eleven patients (44%) achieved a complete response and 7 (28%) achieved a partial response. However, 7 of 25 patients (28%) were considered nonresponders. Median trough adalimumab serum levels were higher in responders than in nonresponders (P < 0.001). We observed AAA positivity (AAA+) at least 1 time point in 8 of 25 patients (32%), including 4 with transitory AAA and 4 with permanent AAA. In all patients with permanent AAA+, trough adalimumab levels became undetectable (P < 0.001). However, in patients who demonstrated transitory AAA+, no correlation was observed between AAA titers and adalimumab trough levels (P = 0.2).Concomitant immunosuppression did not show any protective effect on adalimumab immunogenicity in our cohort. An association between the presence of AAA+ and a worse uveitis outcome was observed only in patients with permanent AAA+, which correlated with undetectable adalimumab trough levels (P = 0.014).



Treatment of noninfectious uveitis with adalimumab is associated with high rates of favorable clinical response. Overall, adalimumab trough levels were higher in responder patients. Development of permanent AAA was associated with undetectable trough adalimumab levels and worse uveitis outcome. Immunogenicity was more common in patients in whom uveitis was associated with a systemic disease and was not influenced by concomitant immunosuppressors.
Uveitis Unit, Department of Ophthalmology, University Hospital of León, León, Spain; Instituto de Biomedicina (IBIOMED), University of León, León, Spain.
Miguel
M
Cordero-Coma
Immunology Service and Uveitis Unit, University Hospital of León, León, Spain.
Sara
S
Calleja-Antolín
Uveitis Unit, Department of Ophthalmology, University Hospital of León, León, Spain.
Irene
I
Garzo-García
Immunology Service and Uveitis Unit, University Hospital of León, León, Spain.
Ana M
AM
Nuñez-Garnés
Rheumatology Service, University Hospital of León, León, Spain.
Carolina
C
Álvarez-Castro
Uveitis Unit, Department of Ophthalmology, University Hospital of León, León, Spain.
Manuel
M
Franco-Benito
Instituto de Biomedicina (IBIOMED), University of León, León, Spain; Immunology Service and Uveitis Unit, University Hospital of León, León, Spain. Electronic address: jgarcir@gmail.com.
Jose G
JG
Ruiz de Morales
D000068879:Adalimumab / Q000276:immunology / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000917:Antibody Formation / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D016896:Treatment Outcome; D014605:Uveitis / Q000097:blood* / Q000188:drug therapy*; D014792:Visual Acuity
D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; D000068879:Adalimumab