Therapeutic blockade of interleukin-6 by tocilizumab in the management of AA amyloidosis and chronic inflammatory disorders: a case series and review of the literature.

Abstract

OBJECTIVES:

AA amyloidosis is the most serious potential complication of chronic inflammatory disorders. The main aim of treatment is to suppress inflammation thereby inhibiting serum amyloid A protein (SAA), which is the precursor of AA amyloid fibrils, to prevent or halt amyloid deposition. Interleukin (IL)-6 blockade is frequently effective in inflammatory conditions, however, there are few published data on its use in AA amyloidosis or the systemic autoinflammatory diseases (SAIDs) or chronic inflammatory conditions. We assessed clinical and serological responses and adverse events associated with tocilizumab (TCZ) use in 20 adult patients with inflammatory disorders refractory to other treatments, including 70% with AA amyloidosis and four with renal transplants.

METHODS:

In addition to routine haematology and biochemistry (including SAA) blood panels, patients with AA amyloidosis underwent SAP scintigraphy to quantify amyloid load. Those with SAIDs underwent genetic analysis to identify mutations/variants in known associated genes. Quality of life (QoL) was surveyed using SF-36v2®.

RESULTS:

Whole-cohort median pre-treatment SAA fell from 70 to 4 mg/L within 10 days of the first dose; this response has been maintained over an on-treatment follow-up period of 23 months (p<0.0001). AA amyloid deposits either regressed or remained stable. QoL improved in several domains. Infections were the predominant adverse effect experienced, but none resulted in permanent discontinuation of therapy.

CONCLUSIONS:

This small series shows that in patients with treatment-refractory chronic inflammatory conditions TCZ can be effective in suppressing inflammation, and in those with AA amyloidosis, can lead to regression of amyloid deposits. Longer follow-up is required to determined long-term safety and efficacy in these conditions.

• Authors: Thirusha Lane, Julian D Gillmore, Ashutosh D Wechalekar, Philip N Hawkins, Helen J Lachmann
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2015 Nov-Dec Vol. 33 Issue 6 Suppl 94 Pg. S46-53 ISSN: 0392-856X [Print] Italy
• PMID: 26120866 (Publication Type: Journal Article, Review)

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Monoclonal, Humanized
• Biomarkers
• IL6 protein, human
• IL6R protein, human
• Interleukin-6
• Receptors, Interleukin-6
• Serum Amyloid A Protein
• tocilizumab

Topics

• Adolescent
• Adult
• Amyloidosis (blood, diagnosis, drug therapy, immunology)
• Anti-Inflammatory Agents (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Biomarkers (blood)
• Child
• Chronic Disease
• Databases, Factual
• Down-Regulation
• Female
• Humans
• Immunocompromised Host
• Inflammation (blood, diagnosis, drug therapy, immunology)
• Interleukin-6 (antagonists & inhibitors, immunology, metabolism)
• Male
• Middle Aged
• Opportunistic Infections (chemically induced, diagnosis, immunology)
• Quality of Life
• Receptors, Interleukin-6 (antagonists & inhibitors, immunology, metabolism)
• Remission Induction
• Risk Factors
• Serum Amyloid A Protein (metabolism)
• Signal Transduction (drug effects)
• Surveys and Questionnaires
• Time Factors
• Treatment Outcome
• Young Adult