Defining a therapeutic range for adalimumab serum concentrations in the management of pediatric noninfectious uveitis, a step towards personalized treatment.

BACKGROUND: Adalimumab is currently considered the most efficacious anti-TNFα agent for childhood noninfectious uveitis (NIU). The objective of this study was to define a therapeutic range for adalimumab trough levels in the treatment of childhood NIU. METHODS: A retrospective, observational, pilot study of 36 children with NIU aged < 18 years, treated with adalimumab. Serum adalimumab through levels and adalimumab anti-drug antibodies (ADA) were analysed at least 24 weeks after start adalimumab. RESULTS: Adalimumab trough levels were significantly higher in complete responders 11.8 µg/mL (range 6.9-33.0) compared to partial or non-responders 9,2 µg/mL (range 0-13.6) (p = 0,004). Receiver-operator characteristics analyses with an area under the curve of 0,749 (95% CI, 0,561-0,937) defined 9.6 µg/mL as the lower margin for the therapeutic range. This cut-off corresponds with a sensitivity of 88% and a specificity of 56% (positive predictive value, 85%; negative predictive value, 62.5%). A concentration effect curve defined 13 µg/mL as the upper margin. Approximately one-third (30.5%) of patients had an adalimumab trough concentration exceeding 13 µg/mL. Free ADA were observed in 2 patients (5.5%). CONCLUSIONS: A therapeutic range of adalimumab trough levels of 9.6 to 13 µg/mL, which corresponds with an optimal clinical effect, was identified. Therapeutic drug monitoring may guide the optimisation of treatment efficacy in children with NIU in the treat-to-target era.

Concurrent Ocular and Cerebral Toxoplasmosis in a Liver Transplant Patient Treated with Anti-CD40 Monoclonal Antibody.

Toxoplasma gondii, an obligate intracellular parasitic protozoon, usually causes a mild, acute infection followed by a latent asymptomatic phase with tissue cysts or a chronic form with recurrent retinochoroiditis. However, immunocompromised patients can cause disseminated disease due to the reactivation of the latent tissue cysts or due to a primary infection. Here, we present a rare case of bilateral ocular toxoplasmosis and concurrent subacute toxoplasma encephalitis in a 70-year-old patient on anti-CD40 treatment following his liver transplant. The diagnosis was confirmed by PCR of anterior chamber fluid and brain biopsy, and no other sites of disseminated disease were detected on PET-CT. The patient has been treated with sulfamethoxazole-trimethoprim 800/160 mg with virtually complete resolution of the neurological and ocular symptoms. Iatrogenic blockade of the CD40 pathway may elicit a particular susceptibility for CNS reactivation of T. gondii.

Unilateral proptosis and blindness caused by meningioma in a patient treated with cyproterone acetate.

Cyproterone has antiandrogenic, antigonadotropic, and progestagenic activity. High-dose preparations are used for treatment of prostate cancer and for treatment of hypersexuality. We describe a patient who was referred to our clinic with slowly progressive unilateral proptosis and blindness of the left eye. He had been treated with high-dose cyproterone actate (CPA) for 23 years. An obvious proptosis and exodeviation of his left eye was noted on ophthalmic examination. Fundoscopy showed left optic atrophy. The literature suggests a link between long-term high-dose exogenous progesterone agonist exposure and the progression and/or development of meningioma. MRI of the brain was performed and revealed multiple meningiomas. One large meningioma located in the anterior temporal lobe extended into the left orbit and caused the proptosis and blindness. Treatment with CPA was stopped and follow-up imaging 11 months later showed a significant decrease in size of the largest meningiomas.