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.
Y. Okuda et al. Arthritis Rheum. 54:2997-3000, 2006
D. Kishida, Y. Okuda et al. Mod Rheumatol. 21:215-218, 2011
Y Okuda et al. Challenges of Rheumatology INTECH. 155-168, 2011
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
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.