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

Official title

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.

Overview

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.

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.

Interventions

• 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.

Primary outcome measures

• Uveitis control [Time frame: 3 months]

Secondary outcome measures (4)

• Best corrected visual acuity (BCVA) [Time frame: 3 months]
• Extent of vascular leakage [Time frame: 3 months]
• BOS 24 score [Time frame: 3 months]
• Uveitis deterioration [Time frame: 3 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

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. PMID 27602665
• 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. PMID 24359625
• 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 Behcet Network. Efficacy of anti-TNF alpha in severe and/or refractory Beh PMID 26162757
• Kaburaki T, Namba K, Sonoda KH, Kezuka T, Keino H, Fukuhara T, Kamoi K, Nakai K, Mizuki N, Ohguro N; Ocular Behcet Disease Research Group of Japan. Behcet'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. PMID 24482146

Identifiers

NCT: NCT05105347 · 42-ZS-2925

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗