Background Many reports have been published in recent years on the usefulness of anti-cytokine therapy in AA amyloidosis in rheumatic disease but, to date, no reports have been published that directly compare the utility of TNF inhibition to that of IL-6 inhibition.
Objectives We retrospectively compared the efficacy and safety of tocilizumab (TCZ) and anti-TNF therapy (TNF) in AA amyloidosis in rheumatic disease at our hospital.
Methods Of the 42 patients studied who were receiving anti-cytokine agents, 31 were receiving a single agent, 10 were receiving 2 agents, and 1 was receiving 3 agents. The patients were divided into 2 groups, a TCZ group (22 patients) and a TNF group (32 patients, 20 of whom received etanercept, 10 infliximab, and 2 adalimumab), and the two groups were compared using the following parameters: (1) treatment retention rate (Kaplan-Meier method) and reasons for withdrawing, (2) SAA profile (mcg/dl, median), (3) change in the eGFR (ml/min/1.73 m2, median), (4) proteinuria profile, and (5) severe gastrointestinal lesions.
Results In the TCZ group, the 1-year retention rate was 90.4%; the 5-year retention rate was 90.4% as well. Two of the 22 patients withdrew, both due to adverse reactions (lower gastrointestinal perforation and cellulitis of the lower leg). In the 32 patients in the TNF group, the 1-year retention rate was 69.0% and the 5-year retention rate was 34.3%. The 14 patients who withdrew did so due to: primary non-response (2 patients), secondary non-response (7 patients), adverse reactions (5 patients [cancer (2 patients; esophageal cancer, malignant lymphoma], hypersensitivity vasculitis [1 patient], lower gastrointestinal perforation [1 patient], COP pattern IP). The retention rate was significantly higher in the TCZ group (log-rank test: p=0.0154). The SAA fell from 219.2 mcg/dl at treatment initiation to 5.0 mcg/dl at the last observation in the TCZ group and from 143.6 mcg/dl at treatment initiation to 38.1 mcg/dl at the last observation in the TNF group, and therefore decreased significantly more in the TCZ group (p=0.0194) (median observation period: 22.5 months in the TCZ group and 21.0 months in the TNF group). The eGFR increased from 41.6 ml/min/1.73 m2 at treatment initiation to 50.7 ml/min/1.73 m2 at the last observation in the TCZ group and decreased from 76.3 ml/min/1.73 m2 at treatment initiation to 67.4 ml/min/1.73 m2 at the last observation in the TNF group. Therefore, although TCZ treatment was initiated at a more advanced stage, significant improvement in renal function was obtained (p=0.0062). In the TCZ group, proteinuria was found in 13 patients at treatment initiation and, at the last observation, 9 had turned negative (median observation period: 31 months). In the TNF group, proteinuria was found in 3 patients, and 1 patient turned negative (median observation period: 10 months). Severe gastrointestinal lesions were found in 1 patient in the TCZ group and 3 patients in the TNF group.
Conclusions We found that TCZ offered greater clinical utility than TNF in AA amyloidosis in rheumatic disease.
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Disclosure of Interest Y. Okuda Grant/Research support from: the Intractable Disease Division of the Ministry of Health and Welfare of Japan, a Research Committee for Amyloidosis in Japan, M. Ohnishi: None Declared, K. Takasugi: None Declared