Anti-TNF treatment in secondary amyloidosis

V. Ortiz-Santamaria, M. Valls-Roc, M. Sanmartí and A. Olivé

Rheumatology Section, Germans Trias i Pujol University Hospital, Barcelona, Spain

Correspondence to: V. Ortiz-Santamaria, Rheumatol-ogy section, Germans Trias i Pujol University Hospital, Carretera de Canyet s/n, Badalona 08916, Barcelona, Spain. E-mail: 33144vos{at}comb.es

SIR, The efficacy of biological therapies in rheumatoid arthritis (RA) [1, 2], ankylosing spondylitis (AS) [3] and psoriatic arthritis [4] is well known. Other diseases, such as Wegener's granulomatosis [5] and Still's disease [6] are currently being evaluated, but the hypothetical benefit in secondary amyloidosis (AA) related to rheumatic diseases has still to be considered. We report our experience with infliximab therapy for AA in our rheumatology service. Patients received infliximab through a compassionate use programme, and informed consent was obtained from every patient. Ethical committee approval was not necessary.

Six patients (three males and three females) with AA (related to RA in five cases and AS in one case) received infliximab (3 mg/kg). Their mean age was 59.3 ± 13.63 yr (range 51–76 yr) and mean time since diagnosis of RA or AS when AA was diagnosed was 12 ± 5 yr (6–20 yr). The clinical manifestation of AA was proteinuria in four cases and/or renal failure in three cases. Diagnosis of AA was performed by rectal (four cases), kidney (three cases) and/or abdominal fat aspiration biopsy (one case). Three patients were withdrawn from infliximab therapy in the first 2 months: two patients because they required haemodialysis and one patient because of an anaphylactoid reaction with respiratory acidosis during the fourth scheduled administration of infliximab, which was administered as monotherapy because of methotrexate intolerance.

Table 1 shows the follow-up of the remaining three patients. Their mean follow-up was 18 ± 9.16 months (range 10–28 months). In patient A, the number of painful and swollen joints improved. Acute-phase reactants improved in the first 22 months and increased during the last 6 months of follow-up, without reaching baseline values. Serum creatinine was slightly increased, but the values remained below 2 mg/dl, and proteinuria did not increase. In patients B and C, the number of painful and swollen joints, serum creatinine and proteinuria improved. Acute-phase reactants improved in patient C. In patient B at month 16, there were no significant changes in the erythrocyte sedimentation rate, but C-reactive protein improved slightly compared with baseline values. It is known that the most important prognostic factor for preventing renal failure in AA is baseline renal function [7]. Early initiation of therapy, before renal function is impaired, may be determinant when evaluating efficacy.


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TABLE 1. Clinical and laboratory follow-up of patients with AA treated with infliximab

 
Among the patients who required haemodialysis, one developed transient pancytopenia concurrently with renal function impairment, and this was the reason for therapy withdrawal. The other patient did not have any adverse event but infliximab therapy was interrupted because at that time it was not known whether infliximab therapy could be administered to end-stage renal failure patients requiring haemodialysis. Recently Singh et al. [8] reported a woman with RA in haemodialysis who was treated with infliximab. The follow-up was fair and no adverse events were reported.

Biological response modifiers, which act as inhibitors of proinflammatory cytokine activation, may play an important role in AA therapy in patients in whom there is a persistent increase in acute-phase reactants. Multicentre studies are needed to confirm the value of anti-tumour necrosis factor therapy in AA related to rheumatic diseases.

The authors have declared no conflicts of interest.

References

  1. Elliott MJ, Maini RN, Feldmann M et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum 1993;36:1681–90[ISI][Medline]
  2. Lipsky PE, van der Heijde DMFM, St Clair EW et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant Therapy Study Group. N Engl J Med 2000;343:1594–602[Abstract/Free Full Text]
  3. Kruithof E, Van der Bosch F, Baeten D, Herssens A et al. Repeated infusions of infliximab, a chimeric anti-TNFalpha monoclonal antibody, in patients with active spondyloarthropathy: one year follow up. Ann Rheum Dis 2002;61:207–12[Abstract/Free Full Text]
  4. Mease PJ. Tumor necrosis factor (TNF) in psoriatic arthritis: pathophysiology and treatment with TNF inhibitors. Ann Rheum Dis 2002;61:298–304[Abstract/Free Full Text]
  5. Stone J, Uhlfelder M, Hellmann D, Crook S, Bedocs N, Hoffman G. Etanercept in Wegener's granulomatosis: a six month open-label trial to evaluate safety. Arthritis Rheum 2000;43 (Suppl.):S404
  6. Husni ME, Maier AL, Mease PJ et al. Etanercept in the treatment of adults patients with Still's disease. Arthritis Rheum 2002;46:1171–6[CrossRef][ISI][Medline]
  7. Gertz MA, Kyle RA. Secondary systemic amyloidosis: response and survival in 64 patients. Medicine (Baltimore) 1991;70:246–56[ISI][Medline]
  8. Singh R, Cuchacovich R, Huang W, Espinoza LR. Infliximab treatment in a patient with rheumatoid arthritis on hemodialysis. J Rheumatol 2002;29:636–7[ISI][Medline]
Accepted 4 March 2003