Background Behcet's disease is a multisystemic chronic relapsing inflammatory disease, classified among the vasculitides. The aetiology of Behcet's disease is unknown. Several cytokines, among them TNF-α, are involved in the pathogenesis of the disease.
Objectives We aimed to assess efficacy and safety of Adalimumab (ADA) in patients with active Behcet's arthritis not responding to one or more DMARDS and to assess the impact of treatment on the cytokine milieu.
Methods Eligible patients (pts) with active arthritis were enrolled in a 24 weeks single center prospective open-label study. Pts who relapsed within 12 weeks following ADA discontinuation could enter a 3 year extension study. The efficacy was assessed by 68 tender and 66 swollen joint count, patient visual analogue scale (VAS) for pain, physician overall disease activity VAS, health assessment questionnaire (HAQ), Behçet's Disease Current Activity Form (BDCAF), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). TNF-α,IL-1β, IL-6, INF-γ, IL-10 and IL-17a were evaluated at baseline, after 24 and 48 weeks of treatment, by ProcartaPlex Human High Sensitivity – Immunoassay kit. Trough ADA serum levels and anti-drug antibodies were measured at baseline, week 24 and 48.
Results Ten pts (6 females),age (mean, standard deviation –SD) 45 (8.4) years, with a disease duration of 11.6 (10) years, were enrolled and treated with subcutaneous ADA 40mg every 2 weeks for 24 weeks. The results are described in Table1. A statistically significant improvement was observed in swollen joint count, physician VAS and BDCAF and in IL-6 levels, but not in tender joint count or HAQ. Resolution of oral and urogenital ulcers was achieved in all pts. Significant reduction of pain was reported by 40% of pts. No relapse of uveitis or other disease manifestations occurred during the study. The reduction in IL-6 levels correlated with the physician VAS and BDCAF but not with HAQ. No correlation was found between change in IL-10 level and VAS pain. The levels of INF-γ, IL-17A, TNF-α were undetectable in all pts. IL-1β was elevated in 1 patient only. ADA serum trough levels were in the therapeutic range in 7/10 pts. One patient developed high antidrug antibodies titer and ADA serum trough level of 0 with a concomitant increase in VAS pain and IL-6 concentration. Another patient with low ADA trough levels and no antibodies improved after providing ADA weekly. The disease relapsed in 9/10 pts, within 4–6 weeks following ADA interruption, 7 pts enrolled into the extension study.
Conclusions ADA treatment was well tolerated and achieved a significant improvement in arthritis and mucocutaneous manifestations and lowered IL-6 serum concentration in all study pts but only 40% reported significant pain reduction. A subset of pts with insufficient improvement in joint tenderness and generalized pain may require comprehensive pain management besides anti-inflammatory therapy.
Acknowledgements ABBVIE donated the study medication and supported the lab work
Disclosure of Interest None declared