Efficacy and Safety of Adalimumab Plus Medium Dose Oral Glucocorticosteroid for Refractory Behçet's Uveitis

Efficacy and Safety of Adalimumab Plus Medium Dose Oral Glucocorticosteroid for Refractory Behçet's Uveitis, Compared With Adalimumab Plus High Dose Oral Glucocorticosteroid, a Non-inferior, Multi-center, Randomized Controlled Trial.

This study is a multi-center randomized non-inferiority study that aims to observe the short-term (3 months) efficacy and safety of adalimumab plus medium-dose glucocorticosteroid (30mg/d prednisone or equivalent) with slow tapering for recurrent Behçet's uveitis (BU) attack compared with adalimumab plus high-dose glucocorticosteroid (60mg/d prednisone or equivalent) with slow tapering.

Study Overview

• Status: Not yet recruiting
• Conditions: Uveitis
• Intervention / Treatment: Drug: Adalimumab plus different doses of oral glucocorticosteroid

Detailed Description

According to the most recent European League Against Rheumatism (EULAR) recommendation, patients presenting with an initial or recurrent episode of acute sight-threatening uveitis should be treated with high-dose glucocorticoids, infliximab or interferon-α. Adalimumab, another TNFα antagonist, is also considered as an alternative for infliximab and have proved its efficacy in several RCTs in the treatment of non-infectious intermediate, posterior and pan-uveitis. As higher dose glucocorticosteroid have greater side effects, this study aims to evaluate the non-inferior efficacy and safety of adalimumab plus medium-dose glucocorticosteroid compared with adalimumab plus high-dose glucocorticosteroid (and slow tapering) for recurrent posterior or pan-uveitis attack of Behcet's uveitis. Refractory BU is defined as relapse of posterior or panuveitis with at least 10mg daily prednisone (or equivalent). The acute attack will be controlled with adalimumab (80mg once, 40mg q2w thereafter) plus medium dose initial oral glucocorticosteroid (30mg daily prednisone or equivalent) in the "medium dose" group or plus high dose oral glucocorticosteroid (60mg daily prednisone or equivalent) in the "high dose" group with fixed tapering protocols. Patients will be followed up at 2w, 4w, 8w, and 12w after initiation of treatment. The primary endpoint is the inflammatory control rate. Secondary endpoints are BCVA, vascular leakage score on fundus fluorescein angiography (FFA), BOS 24 score and uveitis deterioration rate. The safety profiles of both groups will be also monitored.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hang Song, MD; Phone Number: +8615600612346; Email: songhang_pumch@163.com
• Study Contact Backup: Name: Chan Zhao, MD; Phone Number: +8613810454083; Email: zhaochan@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Behçet's disease (BD) patients fulfilling the International Criteria for Behçet's disease (ICBD) published in 2013 with recent recurrence of pan- or posterior uveitis
• The patient should be on ≥10mg/d oral prednisone or equivalent

Exclusion Criteria:

• Previous treatment with TNFα inhibitors within 3 months
• Pregnancy, breast feeding women
• Malignancy
• Heart failure
• Demyelinating diseases
• Renal impairment (creatinine > 1.5 mg/dl)
• Depression or other psychic disorders
• History of acute or chronic inflammatory joint or autoimmune disease
• Patients with severe extra-ocular involvement other than oral/genital ulcer and skin involvement
• Organ or bone marrow transplant recipient, cardiac failure > NYHA III
• Acute liver disease with ALT or SGPT 2x above normal
• White blood cell count < 3500/mm^3
• Platelet count < 100000/mm^3
• Hgb < 8.5g/dl
• T-SPOT TB: ≥200 SFCs per 10^6 PBMC
• Active peptic ulcer, systemic or local infection, moderate to severe osteoporosis or other contraindications of intermediate dose corticosteroids
• Other severe ocular diseases or intraocular surgery within 3 months
• Media opacity precluding a clear view of the fundus
• Positive screen test for HBV, HCV, HIV infection or syphilis
• Body weight <45 kg
• Alcohol abuse or drug abuse
• Mental impairment
• Uncooperative attitude

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medium dose group (Adalimumab plus medium dose oral glucocorticosteroid); Patients will be given adalimumab with 30mg daily prednisone or equivalent with a fixed slow tapering plan.	Drug: Adalimumab plus different doses of oral glucocorticosteroid; A loading dose of 80mg adalimumab will be given subcutaneously and then change to 40mg adalimumab every two weeks. Medium dose oral glucocorticosteroid (30mg/d prednisone or equivalent) will be given to the experimental dose group and high dose oral glucocorticosteroid (60mg/d prednisone or equivalent) will be given to the high dose group.; Other Names: Humira, prednisone
Active Comparator: High dose group (Adalimumab plus high dose oral glucocorticosteroid); Patients will be given adalimumab with 60mg daily prednisone or equivalent with a fixed slow tapering plan.	Drug: Adalimumab plus different doses of oral glucocorticosteroid; A loading dose of 80mg adalimumab will be given subcutaneously and then change to 40mg adalimumab every two weeks. Medium dose oral glucocorticosteroid (30mg/d prednisone or equivalent) will be given to the experimental dose group and high dose oral glucocorticosteroid (60mg/d prednisone or equivalent) will be given to the high dose group.; Other Names: Humira, prednisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uveitis control	Inflammation control according to SUN criteria (two steps decrease of anterior chamber cell or vitreous haze or decreased to zero) or active retinal lesion recession with vitreous haze less than 0.5 grade	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best corrected visual acuity (BCVA)	BCVA was transformed into logMar form	3 months
Extent of vascular leakage	Vascular leakage was quantified based on the method developed by the Angiography Scoring for Uveitis Working Group (ASUWOG), in which vascular leakage in the posterior pole and in each peripheral quadrant was scored 1 if limited	3 months
BOS 24 score	BOS 24 scoring system refers to article "Behc et's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab	3 months
Uveitis deterioration	Inflammation deterioration according to SUN criteria (two steps increase of anterior chamber cell or vitreous haze or increases to grade 4) or new active retinal lesions or new onset of retinal vasculitis	3 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, Chu DS, Camez A, Kwatra NV, Song AP, Kron M, Tari S, Suhler EB. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med. 2016 Sep 8;375(10):932-43. doi: 10.1056/NEJMoa1509852.
• Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A, Van Gelder RN. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology. 2014 Mar;121(3):785-96.e3. doi: 10.1016/j.ophtha.2013.09.048. Epub 2013 Dec 17.
• Vallet H, Riviere S, Sanna A, Deroux A, Moulis G, Addimanda O, Salvarani C, Lambert M, Bielefeld P, Seve P, Sibilia J, Pasquali J, Fraison J, Marie I, Perard L, Bouillet L, Cohen F, Sene D, Schoindre Y, Lidove O, Le Hoang P, Hachulla E, Fain O, Mariette X, Papo T, Wechsler B, Bodaghi B, Rigon MR, Cacoub P, Saadoun D; French Behçet Network. Efficacy of anti-TNF alpha in severe and/or refractory Behçet's disease: Multicenter study of 124 patients. J Autoimmun. 2015 Aug;62:67-74. doi: 10.1016/j.jaut.2015.06.005. Epub 2015 Jul 8.
• Kaburaki T, Namba K, Sonoda KH, Kezuka T, Keino H, Fukuhara T, Kamoi K, Nakai K, Mizuki N, Ohguro N; Ocular Behçet Disease Research Group of Japan. Behçet's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab. Jpn J Ophthalmol. 2014 Mar;58(2):120-30. doi: 10.1007/s10384-013-0294-0. Epub 2014 Jan 31.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 10, 2021
• Primary Completion (Anticipated): December 31, 2026
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: October 19, 2021
• First Submitted That Met QC Criteria: November 1, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

• Last Update Posted (Actual): November 3, 2021
• Last Update Submitted That Met QC Criteria: November 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Uveitis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Adalimumab; Prednisone
• Other Study ID Numbers: 42-ZS-2925

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: email contact person if needed

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No