Background Takayasu arteritis (TA) is an inflammatory large-vessel panarteritis resulting in vessel stenosis, occlusion or aneurysm formation1. Medical therapy with steroids and immunosuppressive agents is the cornerstone of TA although a significant proportion of patients (pts) are refractory to these regimes1. Observations on small groups of TA pts suggest the efficacy of tocilizumab (TCZ), a humanized anti-IL6 receptor antibody2-4, although vascular progression on TCZ despite good clinical and laboratory response has been described4.
Objectives Evaluation of safety and efficacy of TCZ in the treatment of refractory TA.
Methods We retrospectively studied 7 pts with active refractory TA treated with TCZ between 2010 and 2012 at a single academic Italian center. Treatment efficacy was evaluated as: 1) reduction of signs and symptoms of active disease, 2) steroid-sparing activity, 3) vascular lesions evolutions assessed with angio-MRI ad ultrasonography, 4) lowering of inflammatory markers (CRP and ESR).
Results Our 7 pts were all female. Median FU on TCZ was 14 months (IQR 10-20). At baseline, median disease duration was 66 months (IQR 17-82) and the median number of unsuccessful immunosuppressive agents was 4 (IQR 2-6); 4 patients had been previously treated with TNF-inhibitors. Four of the 7 pts responded on TCZ: 3 had a complete response (CR: absence of imaging progression and features of active TA for at least 6 months5 while on prednisone ≤ 7,5 mg/day) and one had partial response (clinical improvement allowing PD reduction >50%). Imaging analysis confirmed these results: four pts (three of whom had CR) did not develop new lesions and in three subjects all lesions remained stable or improved. Threepts developed at least one new lesion and two had also worsening lesions. PD dose was not significantly reduced on TCZ. ESR and CRP levels were consistently reduced in all pts, thus failing to detect the ones with vascular progression. Threepts suspended TCZ for lack of efficacy and two for adverse events (one for recurrent pneumonia and one for severe maculopapular rash).
Conclusions 4 of our 7 pts responded to TCZ. TCZ could thus be a valuable option for refractory TA. However, vascular progression occurred despite good laboratory response and before clinical signs and symptoms of disease activity were evident. We thus suggest that disease monitoring on TCZ should include rigorous imaging evaluation. Further study are necessary for better defining TCZ role in TA therapy.
Mason JC. Takayasu arteritis-advances in diagnosis and management. Nat Rev Rheumatol 2010;6(7):406-15.
Seitz M, Reichenbach S, Bonel HM, Adler S, Wermelinger F, Villiger PM. Rapid induction of remission in large vessel vasculitis by IL-6 blockade. A case series. Swiss Med Wkly 2011;141:w13156.
Salvarani C, Magnani L, Catanoso MG, et al. Rescue treatment with tocilizumab for Takayasu arteritis resistant to TNF-alpha blockers. Clin Exp Rheumatol 2012;30(1 Suppl 70):S90-3.
Bredemeier M, Rocha CM, Barbosa MV, Pitrez EH. One-year clinical and radiological evolution of a patient with refractory Takayasu’s arteritis under treatment with tocilizumab. Clin Exp Rheumatol 2012;30(1 Suppl 70):S98-100.
Molloy ES, Langford CA, Clark TM, Gota CE, Hoffman GS. Anti-tumour necrosis factor therapy in patients with refractory Takayasu arteritis: long-term follow-up. Ann Rheum Dis 2008;67(11):1567-9.
Disclosure of Interest: None Declared