Objective To assess safety and efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK). Methods and Results Two-hundred nine patients with TAK [median age of 29 years [7–62], and 186 (89%) females] were included. They received either TNF-α antagonists [n = 132 (63%) with 172 lines; infliximab (n = 109), adalimumab (n = 45), golimumab (n = 8), certolizumab (n = 6) and etanercept (n = 5)], or tocilizumab [n = 77 (37%) with 121 lines; intravenous and subcutaneous in 95 and 26 cases, respectively]. A complete response at 6 months was evidenced in 101/152 (66%) on TNF-α antagonists and 75/107 (70%) on tocilizumab, respectively. Age ≥ 30 years [OR = 2.09 [1.09; 3.99]] was associated with complete response, whereas vascular signs [0.26 [0.1; 0.65]], baseline prednisone ≥ 20 mg/day [0.51 [0.28; 0.93]] were negatively associated with the complete response to TNF-α antagonists or tocilizumab. During a median follow-up of 36 months, 103 relapses were noted. Supra-aortic branches and thoracic aorta involvements [HR 2.44 (1.06; 5.65) and 3.66 (1.18; 11.4), respectively], and systemic signs at baseline [HR 2.01 (1.30; 3.11)] were significantly associated with relapse. The cumulative incidence of treatment discontinuation and relapse were similar in TNFα antagonists and tocilizumab. Fifty-eight (20%) adverse effects occurred on biological-targeted therapies of whom 37 (21%) and 21 (17%), (p= 0.4) on TNF-α antagonists and tocilizumab, respectively. Conclusion This large multicentre study shows high efficacy of biological-targeted treatments in refractory TAK. Efficacy, relapse and drug retention rate were equivalent with TNF-α antagonists and tocilizumab.

Objective Lysyl oxidase (LOX) is an extracellular enzyme that cross-links collagen fibrils. LOX was found to be increased in serum of SSc patients and was suggested to be related to skin fibrosis, yet a vascular source of LOX has been demonstrated in idiopathic pulmonary arterial hypertension (iPAH). We aimed to validate elevated LOX serum levels in SSc and to study its correlation with clinical characteristics and investigate its main source at the tissue level. Methods A total of 86 established SSc patients were compared with 86 patients with very early diagnosis of systemic sclerosis (VEDOSS), 110 patients with primary RP (PRP) and 80 healthy controls. LOX serum levels were determined by ELISA. Five lung and 12 skin biopsies from SSc patients were stained for LOX and compared with controls. Results Serum levels of LOX in SSc were significantly higher than in VEDOSS, PRP and healthy controls (P < 0.001). LOX inversely correlated with the diffusing capacity of the lung for carbon monoxide diffusing capacity (DLCO) in diffuse SSc (r = −0.376, P = 0.02). Patients with moderate to severe estimated systolic PAH had higher LOX levels (P < 0.01). Lung biopsies demonstrated intense LOX staining in SSc patients with PAH that was predominantly located in the endothelium of the remodelled pulmonary vessels. Conclusion Serum LOX levels are increased in established SSc and inversely correlate with the DLCO. LOX is elevated in patients with moderate to severe PAH and is located in the proliferating endothelium in lung arterioles, suggesting a possible role for LOX in SSc-associated PAH.

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