Clinical trial NCT05105347: 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.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Uveitis
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2021-11-03
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Uveitis control
timeFrame: 3 months
Secondary outcomes:
measure: Best corrected visual acuity (BCVA)
timeFrame: 3 months
measure: Extent of vascular leakage
timeFrame: 3 months
measure: BOS 24 score
timeFrame: 3 months
measure: Uveitis deterioration
timeFrame: 3 months
Other outcomes:
Locations:
Study officials:
References:
citation: 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.
citation: 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.
citation: 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 Behcet'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.
citation: 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.