Long-term TNF-α Blockade in Patients with Amyloid A Amyloidosis Complicating Rheumatic Diseases

doi:10.1016/j.amjmed.2009.11.010

The American Journal of Medicine

Volume 123, Issue 5, May 2010, Pages 454-461

https://doi.org/10.1016/j.amjmed.2009.11.010 Get rights and content

Abstract

Objective

To evaluate the effectiveness and safety of anti-tumor necrosis factor therapy in patients with amyloid A amyloidosis.

Methods

Multicenter, controlled, dynamic prospective cohort study of 36 patients with amyloid A amyloidosis (94% kidney involvement) treated with anti-tumor necrosis factor agents (drug exposure of 102.97 patient-years). As an external control group, 35 propensity score-matched non-amyloid patients were chosen from the Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología registry. The end points were kidney response and progression, anti-tumor necrosis factor continuation rate, patient survival, and adverse events.

Results

At the end of follow-up, a kidney response was observed in 12 of 22 patients (54.5%) and a kidney progression was observed in 6 of 36 patients (17%). The kidney amyloidosis remained stable in 16 of 36 patients (44%). The level of acute phase reactants diminished but did not reach the normal level. The continuation rates of anti-tumor necrosis factor drugs among patients with amyloid A amyloidosis after 1, 2, 3, and 4 or more years were 80%, 80%, 61%, and 52%, respectively, comparable to controls. The 5-year cumulative survival of amyloid A amyloidosis cases was 90.6%, and the 10-year survival was 78.5%. In a multivariate Cox regression analysis, the duration of amyloidosis and the level of proteinuria at the onset of anti-tumor necrosis factor treatment were independent predictors of treatment failure, whereas the level of proteinuria was the only factor that predicts mortality. Most adverse events were similar in both groups, although the number of infections was 3 times higher in amyloid A amyloidosis cases.

Conclusion

Anti-tumor necrosis factor drugs are effective in treating amyloid A amyloidosis, although they might increase the risk of infection.

Section snippets

Patients

The patients included in this study were all patients with amyloid A amyloidosis secondary to an immune-mediated inflammatory disease who were treated and followed up prospectively in 4 Spanish hospitals from January 2001 to October 2006. This study represents an extension of a previous study.⁴ Amyloid A amyloidosis was confirmed histologically by Congo-red staining and immunohistochemistry. Informed consent was obtained from all patients, and the treatment was approved by the local health

Results

From January 1, 2001, to October 31, 2006, a cohort of 36 patients with amyloid A amyloidosis was generated. The patients were treated with anti-tumor necrosis factor drugs for a total of 102.97 patient-years (median follow-up 34.6 months). Thirty-five propensity score-matched control subjects were chosen from the BIOBADASER registry. All patients had highly active immune-mediated inflammatory diseases refractory to other treatments.

Discussion

The present study showed the sustained efficacy of tumor necrosis factor-α antagonists in treating amyloid A amyloidosis secondary to rheumatic diseases. A continuous reduction in proteinuria with this therapy was associated with the stabilization of kidney function and a marked reduction of acute phase reactants. However, both infections and deaths were common.

Having found that tumor necrosis factor-α antagonists might be useful to treat amyloid A amyloidosis in studies with a short follow-up,⁴

Conclusions

We have shown that anti-tumor necrosis factor drugs may be useful to treat kidney amyloidosis but could increase the risk and severity of infections. The long-term follow-up of these patients is essential to define the true effect of these drugs on patient survival. In view of the difficulties in recruiting patients to such trials, multicenter studies would be advisable.

Acknowledgment

The authors thank the rheumatologists who contribute to the BIOBADASER registry.

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: Funding: None. The drugs administered to our patients were supplied by the sanitary service as part of the medical care that they normally received.

: Conflict of Interest: None of the authors have any conflicts of interest associated with the work presented in this manuscript; however, Antonio Fernández-Nebro has earned $1500 or more per year as speaker or consultant (included all companies) for Abbott, Roche, Schering-Plough, and Bristol-Meyer-Squibb companies during the past 3 years, and Rosario García-Vicuña has earned $1500 or more per year as speaker or consultant (included all companies) for Abbott, Roche, Schering-Plough, and Wyeth companies during the past 3 years.

: Authorship: All authors had access to the data and played a role in writing this manuscript. Dr Fernández-Nebro had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design: Fernández-Nebro, García-Vicuña, Olivé. Acquisition of data: Fernández-Nebro, Herranz, Riera, Castro. Analysis and interpretation of data: Fernández-Nebro, García de Yébenes, García-Vicuña, Olivé.

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Clinical research studyLong-term TNF-α Blockade in Patients with Amyloid A Amyloidosis Complicating Rheumatic Diseases

Abstract

Objective

Methods

Results

Conclusion

Section snippets

Patients

Results

Discussion

Conclusions

Acknowledgment

Am J Med

Treatment with TNF blockers and mortality risk in patients with rheumatoid arthritis

Ann Rheum Dis

All-cause and cause-specific mortality in rheumatoid arthritis are not greater than expected when treated with tumour necrosis factor antagonists

Ann Rheum Dis

Anti-tumor necrosis factor alpha therapy in fifteen patients with AA amyloidosis secondary to inflammatory arthritides: a followup report of tolerability and efficacy

Arthritis Rheum

BIOBADASER: Spanish registry of adverse events of biological therapies in rheumatic diseases

Rev Esp Reumatol

Natural history and outcome in systemic AA amyloidosis

N Engl J Med

Invited commentary: propensity scores

Am J Epidemiol

Clinical research study
Long-term TNF-α Blockade in Patients with Amyloid A Amyloidosis Complicating Rheumatic Diseases