• Amyloidosis
• Anti-TNF
• Outcomes research
• DMARDs (biologic)
• DMARDs (synthetic)

Incidence of reactive amyloidosis associated with rheumatic diseases is markedly decreasing1 as the presence of organ failure such as end-stage renal disease.2 However, we still encounter new cases of amyloidosis. While anti-TNF-α therapy may be effective in disease modifying antirheumatic drug (DMARD) resistant cases of amyloidosis, there are yet patients whose disease does not respond to that treatment.3 ,4

We searched for reports on tocilizumab (TCZ), an anti-interleukin-6 receptor (anti-IL-6R) antibody, as treatment for reactive amyloidosis registered in the PUBMED. Altogether six such cases were found with encouraging treatment results.3–8 All the reports are based on single case reports with limited follow-up data. We present over 1-year experience on five patients who were treated with the drug for this indication. One of the patients was included in our preliminary report of the effect of biological drugs on amyloidosis with a short-term experience of TCZ.4

All patients with reactive amyloidosis associated with inflammatory rheumatic diseases treated with TCZ were gathered from four central hospitals in Finland. Five such patients were found whose demographic and clinical data are shown in table 1. In all cases, the analysis of amyloid in tissue specimens was based on Congo red staining. Renal function was assessed by the Cockcroft-Gault formula. In the beginning of TCZ treatment all patients had renal insufficiency which was severe in two. Mean (SD) duration of TCZ treatment was 19.4 (5.0) months. TCZ was administered at a dose of 8 mg/kg once monthly except case No 1 in whom a dose reduction for 4 mg/kg was carried out due to renal insufficiency.

The level of serum C reactive protein (CRP) normalised after the first infusion of TCZ in all of them and the effect was maintained throughout the follow-up period (table 2). TCZ either improved (N=2) or maintained (N=3) the renal function. Proteinuria disappeared in two patients and decreased in one of the four with the finding.

According to our results the efficacy of TCZ in patients with DMARD and anti-TNF-α therapy resistant reactive amyloidosis was excellent also on medium-term basis. While the earlier reports of the efficacy of TCZ in amyloidosis almost exclusively concern patients with severe gastrointestinal manifestation,3 ,5–7 our cases show that TCZ can prevent the progression of renal disease. It is to be noted that the experience from the prebiological era showed that end-stage renal disease due to amyloidosis associated with rheumatic diseases carries a poor prognosis with median survival time of 2–3 years after admittance to renal replacement therapy (dialysis or renal transplantation).9

In the previous decades, chronic infections such as tuberculosis and osteomyelitis were important causes of reactive amyloidosis. However, these infections are now rare in the Western countries. It is to be noted, that four of our patients had had deep tissue infections, either purulent arthritis or wound infections. It can be postulated that prolonged severe infection together with rheumatic inflammation promoted the expression of amyloidosis in these patients.

TCZ showed a rapid and sustained suppression of disease activity—as measured by serum CRP—in our patients. Although we did not measure serum amyloid A (SAA) its level correlates with that of serum CRP in rheumatoid arthritis. The suppression of SAA below 10 mg/l halts the progression of amyloidosis and is strongly associated with a prolonged survival.10

Our results show that medications with anti-IL-6 activity may be helpful in patients with reactive amyloidosis. By its anti-inflammatory effects TCZ even has a potential to prevent progression of amyloidosis associated renal disorder. In this context, its efficacy was also first time shown by medium-term basis.