Adalimumab Treatment in Patients with Vogt-Koyanagi-Harada Disease.
Couto Cristóbal,Schlaen Ariel,Frick Mercedes,Khoury Marina,Lopez Matilde,Hurtado Erika,Goldstein Debra
Ocular immunology and inflammation
PURPOSE:To evaluate the clinical outcome and safety of adalimumab in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS:VKH patients treated with adalimumab seen at the University of Buenos Aires were reviewed. Main outcome measures were visual acuity, anterior segment inflammation, optic nerve inflammation (ONI), steroid sparing effect, number of immunosuppressives, and relapses. RESULTS:In total, 14 VKH patients, mean age 23.07 ± 8 years; median of adalimumab treatment 10 months, were analyzed. At start of adalimumab treatment (baseline), median of corticosteroid dose was 20 mg and at 6 months, 4 mg. At baseline, 11 patients were on immunosuppressive treatment and at 6 months only four continued with immunosuppressive therapy. In the 28 eyes, the median of active inflammation was 2 at baseline and 0 after 6 months on adalimumab. CONCLUSIONS:Treatment with adalimumab is an effective and safe option, reducing the need for oral corticosteroid and conventional immunosuppressive therapy.
10.1080/09273948.2016.1236969
Efficacy and Safety of Adalimumab for Exacerbation or Relapse of Ocular Inflammation in Patients with Vogt-Koyanagi-Harada Disease: A Multicenter Study.
Ocular immunology and inflammation
PURPOSE:We investigated efficacy and safety of adalimumab (ADA) treatment for exacerbation or recurrence of Vogt-Koyanagi-Harada (VKH) patients. METHODS:Medical records of 70 VKH patients who received ADA treatment for more than 6 months were retrospectively investigated. RESULTS:The mean age of VKH patients was 54.8 ± 15.1 years, and male/female ratio was 34/36, and sunset glow fundus was observed in 71.4%. Subfoveal choroidal thickness, indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment for 6 months compared to baseline, while LogMAR and flare counts were also improved without being statistically significant. Adverse events were observed in 17.1%, in which tuberculosis was at 7.14% and psoriasis was at 2.86%; however, ADA treatment was continued in 91.4%. CONCLUSIONS:ADA was shown to be effective to achieve remission of VKH disease refractory to conventional treatments and was generally well tolerated with few serious adverse events.
10.1080/09273948.2022.2092007
Efficacy of Adalimumab for Chronic Vogt-Koyanagi-Harada Disease Refractory to Conventional Corticosteroids and Immunosuppressive Therapy and Complicated by Central Serous Chorioretinopathy.
Takayama Kei,Obata Hiroto,Takeuchi Masaru
Ocular immunology and inflammation
: To report the efficacy of adalimumab in a case of chronic Vogt-Koyanagi-Harada (VKH) disease refractory to conventional corticosteroids and immunosuppressive therapy and complicated by central serous chorioretinopathy (CSC).: A 66-year-old woman diagnosed with VKH was treated with intravenous corticosteroids followed by oral corticosteroids and cyclosporine. However, systemic corticosteroids could not be tapered because of recurrent ocular inflammation and systemic complications (diabetes mellitus, moon face, bone weakness), while CSC appeared in both eyes. A diagnosis of chronic VKH resistant to medications complicated by corticosteroid-induced CSC was made. Systemic corticosteroids and cyclosporine were tapered and adalimumab initiated. Bilateral ocular inflammation and CSC were gradually reduced and visual acuity improved without any adverse effect. Twelve months after starting adalimumab monotherapy, no signs of active VKH and CSC were present.: Adalimumab is one of the effective therapeutic options for refractory VKH disease complicated with corticosteroid-induced adverse effects.
10.1080/09273948.2019.1603312
A randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for Vogt-Koyanagi-Harada disease.
Nature communications
Biologics are increasingly used to treat Vogt-Koyanagi-Harada disease, but head-to-head comparisons with conventional immunosuppressants are lacking. Here in this randomized trial (Chinese Clinical Trial Registry, ChiCTR2100043061), we assigned 110 patients (27 early-phase and 83 late-phase) to cyclosporine-based immunosuppressant strategy (N = 56) or adalimumab-based biologic strategy (N = 54), each combined with a modified corticosteroid regimen. The primary outcome is change from baseline in best-corrected visual acuity at week 26. The margin of non-inferiority for cyclosporine is -7 letters. The primary outcome is 11.2 letters (95% CI, 7.5 to 14.9) in the cyclosporine group and 6.3 letters (95% CI, 3.1 to 9.6) in the adalimumab group (difference, 4.9; 95% CI, 0.2 to 9.5; P < 0.001 for non-inferiority). The between-group difference is -0.8 letters (95% CI, -6.1 to 4.5) in early-phase disease and 5.7 letters (95% CI, 0.2 to 11.2) in late-phase. Serious adverse events are reported less frequently in the cyclosporine group than in the adalimumab group (0.70 vs. 1.21 events per patient-year). Here, we report that combined with a non-standard corticosteroid regimen, cyclosporine-based immunosuppressant strategy is non-inferior to adalimumab-based biologic strategy by 26 weeks for visual improvement in a cohort of patients with Vogt-Koyanagi-Harada disease, 75% of whom have a late-phase disease.
10.1038/s41467-023-39483-5
Clinical and Transcriptional Profiles Reveal the Treatment Effect of Adalimumab in Patients with Initial-Onset and Recurrent Vogt-Koyanagi-Harada Disease.
Ocular immunology and inflammation
PURPOSE:We aimed to evaluate adalimumab efficacy in patients with initial-onset or recurrent Vogt-Koyanagi-Harada (VKH) syndrome. METHODS:A retrospective clinical study was performed to examine the therapeutic effect of adalimumab in 22 VKH patients,16 with initial-onset and six with recurrent VKH. Another 22 patients with initial-onset VKH who did not receive adalimumab were included as controls. The main observational parameters included the central macular thickness (CMT), subfoveal choroidal thickness (SCT), best-corrected visual acuity (BCVA), anterior chamber cell grade (ACC), glucocorticoid dose (GCD), and the development of sunset glow fundus. MRNA sequencing was used to profile the tumor necrosis factor (TNF)-α pathway in peripheral blood mononuclear cells obtained from nine patients with initial-onset VKH disease, six patients with recurrent VKH, and eight healthy controls. RESULTS:In the initial-onset group, adalimumab therapy significantly improved the BCVA, CMT, SCT, and ACC. Furthermore, adalimumab significantly decreased GCD in patients with initial-onset. In patients with recurrent VKH, the SCT significantly improved after adalimumab treatment, but no significant changes in BCVA, CMT, and ACC were observed. All six patients experienced relapse during follow-up. The TNF-α pathway exhibited a significant increase in initial-onset VKH when compared with that in both healthy controls and recurrent patients. Conversely, it was suppressed in recurrent VKH when compared with that in the initial-onset or healthy control groups. CONCLUSIONS:In patients with initial-onset VKH, adalimumab effectively reduces glucocorticoid dependence. However, adalimumab may not be effective for preventing relapse or providing long-term inflammation relief in patients with recurrent VKH.
10.1080/09273948.2024.2346814
Systemic glucocorticoid-free therapy with adalimumab plus immunosuppressants versus conventional therapy in treatment-naïve Vogt-Koyanagi-Harada disease patients.
Annals of translational medicine
Background:High dose systemic glucocorticoid is the main therapy of treatment-naïve Vogt-Koyanagi-Harada (VKH) disease. However, series side effects induced by high dose systemic glucocorticoid frequently occur, which makes alternative therapy necessary for certain patients. This study sought to compare the efficacy and safety of systemic glucocorticoid-free (SGF) therapy with conventional therapy (CT) as an initial treatment for VKH patients. Methods:VKH patients who had not been systemically treated were enrolled. Patients were allocated into 2 therapeutic groups depending on their treatments. In CT group, patients received systemic glucocorticoid plus immunosuppressants (IS), and in SGF group, patients received adalimumab (ADA) plus IS. Patients received approximately 12 months treatment and visit monthly. The outcome parameters included the changes of best-corrected visual acuity (BCVA), intraocular inflammation (including anterior chamber cell grade and vitritis grade) and central macular thickness (CMT) (the change values define as the final-visit values subtracted from baseline counterparts). Other outcomes included the relapses times of ocular inflammation, adverse events (AEs), changes of optic nerve inflammation (ONI) and intraocular/extraocular manifestations. Results:A total of 30 patients (60 eyes) were included. with 19 patients (38 eyes) in CT group and 11 patients (22 eyes) in SGF group. After approximately 1 year of treatment, the improvements of BCVA were slight better in the SGF group (0.57±0.23) than in the CT group (0.40±0.26), (P=0.014). In both groups, the ocular inflammatory improvements in both groups were similar, with an improvement of AC cell grade of -1.5 (-2, -0.5) in CT group versus -1 (-2, -1) in SGF group (P=0.367); improvement of vitritis grade was 0 (-1.25, 0) in CT group and -1 (-1, -1) in SGF group (P=0.050). The improvement in CMT was similar in both groups, with -523.47±412.09 µm in CT group and -362.73±375.73 µm in SGF group (P=0.572). The mean number of relapses was 1 (0, 2) in the CT group and 0 (0, 2) in the SGF group (P=0.372). No severe AEs were observed in this study. Conclusions:SGF therapy is effective, safe, and well-tolerated in treatment-naïve VKH patients. SGF therapy seems to be a feasible option in patients with existing systemic diseases intolerant to glucocorticoid.
10.21037/atm-22-2668
Vogt-Koyanagi-Harada Disease and Systemic Lupus Erythematosus Occurring during Adalimumab Therapy for Ulcerative Colitis.
AlBloushi Abdulrahman F,Al-Hadlaq Omar S,AlRashed Faisal A,Abu El-Asrar Ahmed M
Middle East African journal of ophthalmology
We report the case of a 36-year-old male patient known to have ulcerative colitis on adalimumab treatment for 2 years who presented with initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease. Uveitis was treated successfully with systemic corticosteroids combined with mycophenolate mofetil. The patient had complete resolution of posterior segment inflammation and exudative retinal detachment. One year after the initial presentation, the patient was diagnosed to have systemic lupus erythematosus and adalimumab was discontinued. This case suggests that adalimumab could induce severe autoimmune inflammatory diseases.
10.4103/meajo.MEAJO_238_19
Clinical Characteristics and Efficacy of Adalimumab and Low-Dose Methotrexate Combination Therapy in Patients With Vogt-Koyanagi-Harada Disease.
Frontiers in medicine
This retrospective study investigated the clinical characteristics and efficacy of adalimumab and low-dose methotrexate combination therapy in patients with Vogt-Koyanagi-Harada disease who were treated at Hiroshima University from February 2012 to May 2021. The patients' demographics, clinical features at administration of immunosuppressive therapy, steroid-sparing immunosuppressive therapy, side effects, and relapses were recorded. The efficacies of steroid-sparing immunosuppressive therapy (methotrexate, cyclosporine A, adalimumab, and adalimumab and methotrexate combination therapy) were analyzed. Among 62 patients, the median age at diagnosis was 47 years and the median duration of uveitis was 51 months. Systemic corticosteroid therapy was administered to 93.5% of patients ( = 58). Thirty-four patients (54.8%) were treated with steroid-sparing immunosuppressive therapy. Methotrexate and cyclosporine A were administered to 12 and 22 patients, respectively; relapse occurred in 50.0% and 22.7% of the patients, respectively. Discontinuation of cyclosporine A was required in 63.6% of patients because of side effects. Adalimumab was administered to 14 patients. Recurrence occurred in 11 patients, requiring methotrexate concomitantly. The mean dose of methotrexate at inflammatory quiescence after side effect-related dose decrease was 8.0 mg/week (0.13 mg/kg). The median duration of combination therapy without recurrence was 20 months. There were no serious adverse events during adalimumab therapy. A high relapse rate was observed in patients receiving methotrexate; a high rate of side effects requiring discontinuation was observed in patients receiving Cyclosporine A. Patients with late-stage Vogt-Koyanagi-Harada disease may achieve better control with adalimumab and methotrexate combination therapy.
10.3389/fmed.2021.730215
Adalimumab treatment for chronic recurrent Vogt-Koyanagi-Harada disease with sunset glow fundus: A multicenter study.
Saudi journal of ophthalmology : official journal of the Saudi Ophthalmological Society
PURPOSE:We investigated the efficacy and safety of adalimumab (ADA) treatment for chronic recurrent Vogt-Koyanagi-Harada (VKH) patients with sunset glow fundus (SGF). METHODS:Medical records of 50 chronic recurrent VKH patients with SGF who received ADA treatment for more than 6 months were retrospectively reviewed. RESULTS:The mean age of chronic recurrent VKH patients with SGF was 55.9 ± 14.4 years, and the male/female ratio was 26/24. Before ADA treatment, the mean daily dose of systemic corticosteroids was 16.5 ± 12.7 mg, and 22 patients (44%) were under immunosuppressors. LogMAR visual acuity (VA), flare counts, subfoveal choroidal thickness (SFCT), indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment at 6 months compared to baseline. Among all parameters, flare count was significantly related to LogMAR VA. LogMAR VA was significantly related to flare counts but not to SFCT nor to ICGA scores. ADA treatment was continued in 94%. CONCLUSION:ADA was shown to be effective in achieving remission of chronic recurrent VKH disease with SGF refractory to conventional treatments, and was generally well tolerated with few serious adverse events.
10.4103/sjopt.sjopt_204_22
Adalimumab in Vogt-Koyanagi-Harada Disease Refractory to Conventional Therapy.
Yang Shizhao,Tao Tianyu,Huang Zhaohao,Liu Xiuxing,Li He,Xie Lihui,Wen Feng,Chi Wei,Su Wenru
Frontiers in medicine
No study explores the effectiveness of adalimumab in sight-threatening Vogt-Koyanagi-Harada (VKH) patients in China. To evaluate the short-term effectiveness and safety of adalimumab (ADA) in patients with sight-threatening Vogt-Koyanagi-Harada (VKH) disease refractory to conventional therapy. Medical records of VKH patients who had been treated with systemic glucocorticoids and immunosuppressants but whose condition was poorly controlled were collected and analyzed. Primary outcomes comprised of best-corrected visual acuity (BCVA), intraocular inflammation, relapses, and glucocorticoid-sparing effects. Other outcomes included central macular thickness (CMT), intraocular manifestations and adverse events (AEs). Nine refractory VKH patients with a median age of 30 (16, 43) years old were enrolled in this study and received treatment for a median of 10 (7, 11) months. Mean BCVA improved from LogMar 0.63 ± 0.50 (20/72 or 0.36 ± 0.26 in Snellen chart) at baseline to LogMar 0.50 ± 0.37 (20/82 or 0.41 ± 0.28 in Snellen chart) at final visit ( = 0.090). The anterior chamber cell grade decreased from 2 (1.75, 3)+ at baseline to 0.5 (0, 1.25)+ cell at final visit ( < 0.001). The vitritis grade decreased from 1 (1, 1) + cell at baseline to 0 (0, 1)+ cell at final visit ( < 0.001). Patients suffered a median of 1 (0, 2) relapse during treatment. CMT remained stable from 238.50 ± 144.94 μm at baseline to 219.28 ± 77.20 μm at final visit ( = 0.553). The mean prednisone dosage decreased from 21.91 ± 18.39 mg/d to 2.73 ± 4.10 mg/d ( = 0.005). No severe AEs were found during treatment. The outcomes indicated that ADA was an effective and safe option for VKH patients refractory to conventional therapy by controlling inflammation, preserving visual function and reducing the daily glucocorticoid dose.
10.3389/fmed.2021.799427