Table 1: Studies reporting on patients with Behçet’s disease treated with anti-IL1 agents.

First author (reference, year) ptsClinical and laboratory featuresHLA-B51Previous biologic agents and causes of withdrawalDosage and eventual cotherapiesFollowupOutcome

Botsios (2008) [43]1Fever, mucosal involvement, colon ischemic perforation, necrotizing lymphocytic venulitis, thrombosis, serositis, increase of inflammatory markers, and SPRNegativeIFX: mucosal abdominal abscessesANA 100 mg/day + PDN 5 mg/day20 monthsCR and improvement of inflammatory markers in 7–10 days. Disease-free at 20-month followup

Bilginer (2010) [44]1Fever, mucosal involvement, EN, arthritis, secondary amyloidosis, increase of inflammatory markers, and SPR overlapping with FMFNRNoneANA 1 mg/kg/day18 monthsCR and improvement of inflammatory markers; patient free of clinical symptoms at 18-month followup; however proteinuria gradually increased (from 1,8 to 2,4 g/day)

Gül (2012) [45]7Acute posterior or panuveitis and/or retinal vasculitisNRNoneGEV: 0.3 mg/kg (single infusion)Up to disease relapseImprovement in visual acuity from day 1 in 5 out of 7 patients. Complete resolution of retinal findings achieved in 4–21 days (median 14 days). No detailed assessments of extraocular manifestations were performed. Recurrence of folliculitis and oral aphtosis. Median duration of response: 49 days (range: 21–97 days)

Ugurlu (2012) [46]1Mucosal involvement, EN, bilateral panuveitis, retinal vasculitis, and SPRNRINF-γ: fever;
IFX and ANA: flares of uveitis;
ADA: loss of efficacy
CAN 150 mg (single dose)8 weeksCR for 8 weeks; resolution of ocular inflammation and rapid VA improvement.

Emmi (2013) [47]1Mucosal and gastrointestinal involvement, arthritis, pseudofolliculitis, and bilateral retinal vasculitisNRIFX: ADR (diffuse urticaria with angioedema);
ADA and RTX: persistent uveitis
ANA 100 mg/day12 monthsCR after 12 months of followup; rapid and persistent disappearance of joint pain, mucocutaneous and bowel manifestations; VA improvement, clearing of the vitreous opacity and no active retinal inflammation

Cantarini (2013) [12]9Mucosal involvement, EN, headache, retinal vasculitis, low-back pain, and increase of inflammatory markersPositiveETN and IFX: loss of efficacyANA 150 mg/day +
PDN 25 mg/day +
colchicine 1 mg/day
9 monthsPR; PDN was reduced to 7.5 mg/day
Fever, mucosal involvement, skin lesions, headache, arthritis, abdominal pain, and increase of inflammatory markersPositiveNoneANA 100 mg/day19 monthsCR at 12-month followup;
onset of DVT after 16 months;
CR at 28-month followup
Fever, mucosal involvement, skin lesions, headache, and increase of SAAPositiveANA (100 mg/day): inefficacyANA 150 mg/day +
PDN 25 mg/day
19 monthsDVT not resolved with heparin at 6 months; CYC (5 mg/kg/day) was added;
CR with reduction of SAA at 18 months
Mucosal involvement, bilateral panuveitis, retrobulbar optic neuritis, papillophlebitis, headache, arthralgia, DVT, and increase of SAAPositiveETN: loss of efficacyANA 100 mg/day +
PDN 12.5 mg/day
6 monthsFlare of panuveitis after 3 months; ANA was withdrawn; CR with ADA (40 mg twice monthly) + MTX (10 mg/weekly) + PDN (25 mg/day)
Mucosal involvement, bilateral panuveitis, arthralgia, and increase of inflammatory markersPositiveNoneANA 100 mg/day + AZA 50 mg/day + PDN 7.5 mg/day8 monthsCR after 12 months
Fever, mucosal involvement, venous thrombosis, arthritis, panuveitis, headache, pseudofolliculitis, and increase of ESR and SAAPositiveNoneANA 100 mg/day12 monthsFlare of uveitis after 8 months; ANA was increased to 150 mg/day + MTX (15 mg/weekly) + colchicine (1 mg/day); PR at 17 months of followup
Mucosal involvement, skin lesions, abdominal pain, photophobia, and increase of SAAPositiveADA: inefficacyANA 2 mg/kg/day + PDN 15 mg/day9 monthsCR at first; relapse after 4 months requiring an increased dosage of ANA (2.5 mg/kg/day); PR after 7 months
Fever, mucosal involvement, EN, arthritis, anterior uveitis, pseudofolliculitis, and increase of CRPPositiveNoneANA 100 mg/day +
PDN 10 mg/day
6 monthsPR; CYC (5 mg/kg/day) was added after 8 months of followup
Fever, mucosal and gastrointestinal involvement, headache, anterior uveitis, and arthralgiaPositiveETN and ADA: loss of efficacyANA 100 mg/day9 monthsInefficacy after 8 weeks;
CAN (150 mg every 8 weeks) was started with PR after 2 weeks

Caso (2014) [48]1Mucosal and ocular involvement, pseudofolliculitis, sacroiliitis, and increase of inflammatory markersPositiveIFX: loss of efficacyANA 100 mg/day +
PDN 50 mg/day
12 monthsCR in few days; PDN was tapered to 5 mg/day

Cantarini (2012) [49]
Vitale (2014) [50]
3Fever, mucosal involvement, skin lesions, arthritis, abdominal pain, headache, and increase of inflammatory markers and SAA overlapping with granuloma annularePositiveSSZ, MTX, CYC, AZA and LFN: inefficacy;
ETN: ADR (recurrent urinary tract infections and bacterial endocarditis);
IFX: ADR (recurrent urinary tract infections);
ANA: ADR (urticarial lesions)
CAN 150 mg every 8 weeks16 monthsCR in few months;
DVT after 16 months: heparin was started and CAN dosing interval was shortened to 6 weeks; CR after 6 months of followup
Fever, mucosal and gastrointestinal involvement, headache, anterior uveitis, and arthralgiaPositiveETN and ADA: loss of efficacy; ANA: inefficacyCAN 150 mg every 6 weeks12 monthsCR after few months
Fever, mucosal involvement, DVT, panuveitis, headache, arthritis, pseudofolliculitis, and increase of ESR and SAAPositiveANA: ADR (urticarial skin lesions)CAN 150 mg every 6 weeks6 monthsCR within few days

Abbreviations: ADA: adalimumab; ADR: adverse reactions; ANA: anakinra; AZA: azathioprine; BD: Behcet's disease; CAN: canakinumab; CYC: cyclosporine; CMO: cystoid macular oedema; CR: complete remission; CRP: C-reactive protein; CS: corticosteroids; DVT: deep venous thrombosis; EN: erythema nodosum; ESR: erythrocyte sedimentation rate; ETN: etanercept; FMF: familial Mediterranean fever; GEV: gevokizumab; HLA: human leukocyte antigen; Ig: immunoglobulin; IFX: infliximab; INF- : interferon-gamma; LFN: leflunomide; MTX: methotrexate; : number; NR: not reported; pts: patients; PDN: prednisone; PR: partial remission; RTX: rituximab; SAA: serum amyloid-A; SPR: skin pathergy reaction; SSZ: sulfasalazine; VA: visual acuity.