Background Takayasu's arteritis (TAK) has a prolonged chronic course and requires long-term immunosuppressive treatment with different results. Tumor necrosis factor (TNF) alpha is a promising target for treatment in patients with TAK, though clinical experience is limited. Certolizumab pegol (CER) is a pegylated Fab' fragment of a humanized TNF inhibitor monoclonal antibody.
Objectives To evaluate the efficacy and safety of treatment with CER in patients with TAK refractory to standard immunosuppressive treatment.
Methods Four patients with type 5 [generalized] TAK (all females, median age 30.5 years [20–33]) were treated with CER for the average of 10.5 months (8–12). TAK was diagnosed according to the ACR criteria and CHCC2012. CER was administered subcutaneously at a dosage of 400 mg every 4 weeks (with loading dose 400 mg every 2 weeks for the first month). Prior to CER administration all patients were treated with combination of immunosuppressive drugs (PRED + median 3 cytotoxic agents [MTX=4, MMF=3, CYC=2, LEF=1, AZA=1] and 1 biologic agent [INFL=2, TOCI=1] for 7.5 years [1–12]). Criteria of efficacy included complete and incomplete remission and relapse of arteritis. Activity of disease was evaluated using the NIH criteria and the Indian Takayasu Clinical Activity Score (ITAS2010).
Results Median duration of disease before CER administration was 12 years (11–16). High activity of TAK was confirmed by standard laboratory tests (median ESR 38 mm/h, CRP 21 mg/L) and MR-angiography/US. All patients improved, including complete and partial remission in 3 (75%) and 1 (25%) patients, respectively. Median PRED dose was reduced from 15 mg (10–25) to 5 mg daily (≤5 mg daily in 3 patients, discontinuation in 1). 2 patients discontinued MTX and MMF, in 1 patient MTX dose was decreased from 20 to 10 mg/wk, 1 patient continued CER monotherapy for 6 months. After treatment average ESR and CRP were 10 mm/h and 1.2 mg/L, respectively. Repeated US and MRA confirmed low or absence activity of disease in all patients. Median ITAS score decreased from 4 (2–10) to 0 (0–2) and median Kerr index decreased from 2 (1–3) to 0 (0–1). CER administrations were well-tolerated; we observed 1 case of community-acquired pneumonia (after 4 months of CER) and 1 case of post-operative abscess of foot (after 5 months of CER). During treatment with CER there were no relapses of TAK. All patients continue CER treatment.
Conclusions CER is effective in case of active systemic inflammation in patients with TAK that was refractory to other immunosuppressive therapies, including biologic agents (INFL, TOCI). In one case CER monotherapy was sufficient to control disease activity for at least 6 months. As in case of other TNF inhibitors the risk of infections should be taken into account. Long-term results with clinically important end-points (surgical interventions, occlusions or stenosis progression, long-term survival etc.) are awaited.
Disclosure of Interest None declared