Effective anti-TNF-alpha therapy can induce rapid resolution and sustained decrease of gastroduodenal mucosal amyloid deposits in reactive amyloidosis associated with rheumatoid arthritis.
OBJECTIVE
To examine the effect of anti-tumor necrosis factor-alpha (anti-TNF) therapy in patients with reactive AA amyloidosis associated with rheumatoid arthritis (RA).


METHODS
Fourteen patients with reactive AA amyloidosis associated with RA were prospectively evaluated. Four patients were treated with infliximab and 10 with etanercept. The mean period of anti-TNF therapy was 20.1 +/- 13.8 months. Laboratory findings and renal function were examined before and after initiation of anti-TNF therapy. In 9 patients the area of amyloid deposits in serial gastroduodenal mucosal biopsy specimens was examined and image analysis was performed.


RESULTS
C-reactive protein and serum amyloid A protein levels were significantly reduced after initiation of anti-TNF therapy. Twenty-four hour creatinine clearance improved in 4 patients, did not change in 5, and deteriorated in 3. Twenty-four hour urinary protein excretion was significantly decreased in 3 patients, not exacerbated in 6, and increased in 3 after initiation of anti-TNF therapy. The biopsy specimens from the 9 patients who underwent serial gastroduodenal biopsies showed significant decreases in the area of amyloid deposits, from 8.8% +/- 6.4% to 1.6% +/- 0.6% (p = 0.003) after initiation of anti-TNF therapy. Four patients showed a sustained decrease in the areas of amyloid deposits in their third biopsy specimens, and amyloid deposits were not detectable in 2.


CONCLUSIONS
Our results indicate a striking effect of anti-TNF therapy for rapid removal and sustained disappearance of amyloid deposits in gastric mucosal tissue with amelioration of renal functions in patients with reactive amyloidosis due to RA.
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Cyuo-ku, Niigata, Japan.
Takeshi
T
Kuroda
Yoko
Y
Wada
Daisuke
D
Kobayashi
Shuichi
S
Murakami
Takehito
T
Sakai
Shintaro
S
Hirose
Naohito
N
Tanabe
Takako
T
Saeki
Masaaki
M
Nakano
Ichiei
I
Narita
D000328:Adult; D000368:Aged; D000682:Amyloid / Q000276:immunology; D000686:Amyloidosis / Q000188:drug therapy / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D004386:Duodenum / Q000033:anatomy & histology / Q000473:pathology; D000068800:Etanercept; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D055815:Young Adult
D000682:Amyloid; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept