Long-Term Follow-up of Patients With Uveitis Treated With Adalimumab: Response Rates and Reasons for Discontinuation of Therapy.

PURPOSE: To evaluate the effectiveness and reasons for discontinuation including the side effect profiles of adalimumab in a real-world setting. DESIGN: Retrospective clinical cohort study. METHODS: A medical chart review of clinical practice in 2 tertiary eye care services in Rotterdam, the Netherlands, was performed Data were collected from May 1, 2004, through September 1, 2020. Patients with noninfectious uveitis treated with adalimumab (n = 341; 633 affected eyes) were included. The primary outcome was the effectiveness of adalimumab, measured by the number of patients achieving inactive disease, remission, and relapse-free survival. The secondary outcomes were the reasons for discontinuation, including side effects, and the number of patients who developed antibodies. RESULTS: In total, 341 patients were treated with adalimumab between May 2004 and September 2020. The uveitis recurrence-free survival interval was 3.4 years (range, 0-13 years). Adalimumab had an acceptable side effect profile. A total of 178 patients achieved inactive disease while continuing adalimumab, and 51 patients maintained remission after discontinuing adalimumab. Reasons for discontinuation of adalimumab were no response, relapse, or reasons unrelated to the effectiveness of treatment. Adalimumab antibodies were present in 40 of 115 patients (35%). Antibodies were associated with lower adalimumab levels, and antibodies were observed more often in patients on adalimumab monotherapy (P < .01). CONCLUSIONS: Adalimumab is effective for patients with noninfectious uveitis, with an acceptable side effect profile. Although relapses can occur, the majority of the patients achieved inactive disease or remission after cessation of adalimumab, without other systemic immunosuppressive medication.

Sensitivity and specificity of serum soluble interleukin-2 receptor for diagnosing sarcoidosis in a population of patients suspected of sarcoidosis.

BACKGROUND: The soluble interleukin 2 receptor (sIL-2R) has been proposed as a marker of disease activity in patients with sarcoidosis. However, no studies have evaluated whether serum sIL-2R measurement is of use in establishing the diagnosis of sarcoidosis in patients who are suspected of sarcoidosis among other diseases. METHODS: A cohort study was conducted, consisting of new patients who visited the immunology outpatient clinic and whose serum sIL-2R levels were available before a definitive diagnosis was established between February 2011 and February 2016. All patients underwent standard diagnostic testing for sarcoidosis (e.g. laboratory tests, radiographic and/or nuclear imaging and/or affected site biopsy). This resulted either in the diagnosis of sarcoidosis or the exclusion of sarcoidosis with the diagnosis of another disease. Results of sIL-2R and angiotensin-converting enzyme (ACE) levels, radiographic and nuclear imaging and histology results were collected and definitive diagnoses were recorded. Sensitivity, specificity, the concordance statistic from the receiver operating characteristic curve and Youden's Index were calculated to assess the performance of sIL-2R in the diagnosis of sarcoidosis and were compared to ACE, currently one of the most used diagnostic biomarkers in the diagnosis of sarcoidosis. RESULTS: In total 983 patients were screened for inclusion, of which 189 patients met the inclusion criteria. A total of 101 patients were diagnosed with sarcoidosis after diagnostic workup, of whom 79 were biopsy-proven. In 88 patients a diagnosis other than sarcoidosis was made. The sensitivity and specificity of serum soluble interleukin 2 receptor levels to detect sarcoidosis were 88% and 85%. The sensitivity and specificity of ACE were 62% and 76%. Receiver operating characteristic curve analysis revealed that sIL-2R receptor is superior to ACE (p<0.0001). CONCLUSION: Serum sIL-2R is a sensitive biomarker and superior to ACE in establishing the diagnosis of sarcoidosis and can be used to rule out sarcoidosis in patients suspected of sarcoidosis.

Relevance of erythrocyte sedimentation rate and C-reactive protein in patients with active uveitis.

PURPOSE: To relate erythrocyte sedimentation rates (ESR) and C-reactive protein (CRP) values to different uveitis entisties. METHODS: A retrospective study of patients with a first episode of active uveitis visiting the Erasmus University Medical Center, uveitis clinic, Rotterdam, the Netherlands, was performed. Levels of ESR and CRP were determined within 2 weeks and 1 week after onset of uveitis, respectively. Uveitis had to be of unknown origin at that moment. The specific etiologic groups were related to ESR and CRP values. RESULTS: The majority of patients with uveitis had ESR and/or CRP values within the normal limits and no association of ESR and/or CRP with the specific cause of uveitis was observed. However, elevation of ESR ≥ 60 mm/h and/or CRP ≥ 60 mg/L was mostly seen in patients with systemic immune-mediated diseases (8/59, 14% of all with immune-mediated diseases) or systemic infectious causes (7/38, 18% of all infectious uveitis). Patients with ocular toxoplasmosis typically exhibited normal ESR and CRP (9/11, 82%) while patients with endogenous endophthalmitis had elevated ESR and/or CRP in 6/7, 86%. Sarcoidosis-associated uveitis showed predominantly elevated ESR (13/24, 54%; range 20-59 mm/h in 11/13, 85%). Human immunodeficiency virus-positive patients had more often elevated ESR values when compared to the remainder of patients (9/11, 82% vs. 64/163, 39%, 18%, P = 0.009). The cause of uveitis was established in 19/20 (95%) of patients with ESR ≥ 60 mm/h and/or CRP ≥ 60 mg/L. CONCLUSIONS: The majority of patients with first attack of uveitis had ESR and CRP within the normal limits. Elevated levels of ESR and CRP reflected systemic involvement and high levels of both values were associated with established uveitis cause.

Lymphopaenia as a predictor of sarcoidosis in patients with a first episode of uveitis.

BACKGROUND/AIMS: The diagnostic properties of conventional diagnostic tests (ACE and chest radiography) for sarcoidosis-associated uveitis are not ideal. The diagnostic value of lymphopaenia for sarcoidosis-associated uveitis is investigated. METHODS: A retrospective study of 191 consecutive patients with a first uveitis episode visiting the ophthalmology department (Erasmus Medical Center, Rotterdam, The Netherlands). Receiver operating characteristics (ROC) analysis was performed and compared with known ROC values from literature of conventional diagnostic tests for sarcoidosis-associated uveitis. An ideal cut-off was determined for lymphopaenia by calculation of the highest Youden index. RESULTS: Out of all patients with first uveitis attack, 32/191 or 17% were subsequently diagnosed with biopsy-proven or radiological diagnosis of sarcoidosis. Lymphopaenia (<1.5×109/L) was significantly more often observed in patients with sarcoidosis-associated uveitis compared with patients with non-sarcoidosis-associated uveitis (p<0.05). The sensitivity and specificity of lymphopaenia was 75 % and 77 %, respectively. The optimal cut-off for lymphopaenia for diagnosing sarcoidosis-associated uveitis was 1.47 ×109/L. Lymphopaenia resulted in a 12.0 (95% CI 4.7 to 30.5 fold risk for having sarcoidosis, corrected for sex, race and age at onset of uveitis in patients with a first uveitis attack. CONCLUSION: Lymphopaenia is a non-invasive and useful marker for diagnosing sarcoidosis-associated uveitis.

Diagnostic Value of Serum-Soluble Interleukin 2 Receptor Levels vs Angiotensin-Converting Enzyme in Patients With Sarcoidosis-Associated Uveitis.

Importance: New and improved diagnostic tests for sarcoidosis-associated uveitis are needed because the currently available laboratory diagnostic biomarkers (eg, lysozyme and angiotensin-converting enzyme [ACE]) are lacking in high sensitivity and specificity. Objective: To compare the value of soluble interleukin 2 receptor (sIL-2R) with ACE as diagnostic biomarkers of sarcoidosis in patients with uveitis. Design, Setting, and Participants: A cross-sectional retrospective study was conducted using data collected from 249 consecutive patients with uveitis at the Erasmus University Medical Center uveitis outpatient clinic, Rotterdam, the Netherlands, from April 3, 2013, through November 25, 2015. Measurements of sIL-2R and ACE in serum samples and data extraction from patient files were conducted from December 2016 through February 2017, and analysis from April to May 2017. Main Outcomes and Measures: Serum levels of sIL-2R and ACE and chest radiographic findings were assessed. Receiver operating characteristics analysis was used to determine the probability that individual tests correctly identified patients with sarcoidosis. The Youden Index was used to determine the optimal cutoff points for serum sIL-2R and ACE levels to define sarcoidosis in patients with uveitis. Results: Data were analyzed from 249 patients with uveitis who had their serum sIL-2R and ACE levels determined and underwent chest radiography. Mean (SD) age at the time of sampling was 51 (16) years, 161 patients (64.7%) were women, and 191 (76.7%) were white. Although patients with sarcoidosis-associated uveitis had the highest mean (SD) serum sIL-2R (6047 [2533] pg/mL) and ACE (61 [38] U/L) levels, elevated serum sIL-2R levels were also found in patients with HLA-B27­associated (4460 [2465] pg/mL) and varicella-zoster virus­associated (5386 [1778] pg/mL) uveitis. Serum sIL-2R and ACE levels were significantly correlated (Pearson correlation coefficient, 0.205; P = .001, 2-sided), but no association was found between uveitis activity and sIL-2R (Spearman rank correlation coefficient [ρ], 0.070, P = .27) nor uveitis activity and ACE (ρ, −0.071; P = .27). The highest Youden index for sIL-2R alone was 0.45, corresponding to an optimal cutoff of 4000 pg/mL and providing 81% (95% CI, 74%-89%) sensitivity and 64% (95% CI, 56%-72%) specificity alone but combined with chest radiography yielded 92% sensitivity and 58% specificity. Chest radiography combined with sIL-2R at a cutoff of 6000 pg/mL resulted in 77% sensitivity and 73% specificity. Combined chest radiography and serum ACE levels at the standard cutoff of 68 U/L resulted in 70% sensitivity and 79% specificity. Conclusions and Relevance: This cross-sectional study demonstrates that sIL-2R is a useful marker for diagnosing sarcoidosis in patients with uveitis and has slightly better diagnostic value than ACE.