Anti‐TNF‐α for treatment of amyloidosis associated with Crohn's disease

We wish to comment on the case reported by Iizuka and colleagues (Gut 2006;55:744–5) of a patient who experienced a reduction in creatine levels from 4 to 2 mg/dl after three weeks of treatment with infliximab for amyloidosis associated with Crohn's disease. Unfortunately, no details were provided of other concomitant factors, such as volume depletion or drugs, which may have affected baseline creatinine levels and their later course, irrespective of amyloidosis, or of the results of proteinuria observed in 1992.

In our experience,¹ anti‐TNF‐α therapy has a rapid effect on proteinuria but not on renal function. In our patients it took several months (the most rapid decrease was from 1.6 to 0.94 mg/dl in three months) for serum creatinine levels to decrease by (mean (SD) percentage since baseline) 8.5 (16.6)% (range −21.4 to 39.4) after 70 (44) weeks (range 2–120), and only 36% of patients experienced a 20% reduction or greater.

We should also like to comment on the choice of anti‐TNF for the management of amyloidosis in patients with quiescent Crohn's disease but active spondyloarthropathy.

One of our patients was diagnosed by clinical, endoscopic, and histological criteria with spondyloarthropathy associated with Crohn's disease in 1988 at the age of 20 years. His intestinal disease was moderately active at the beginning whereas his spondyloarthropathy remained highly active, causing severe restriction in the whole spine, shoulders, and hips. He underwent arthroplasty of both hips in 1995 and 1997. In 1998, when his intestinal disease had been inactive for more than five years, he developed nephrotic syndrome (proteinuria of 11.72 g/day and normal renal function). Rectal biopsy was negative but kidney biopsy showed extensive glomerular and arteriolar AA amyloid deposits. At the beginning of 2001 his renal function started to decline and treatment was initiated with etanercept 25 mg, twice weekly, with excellent clinical and analytical results (fig 1). Twelve months later repeated episodes of intestinal activity commenced, with later worsening of the proteinuria and renal function. After 29 months, etanercept was replaced by infliximab (5 mg/kg) but his status continued to worsen despite haemodialysis and ileal resection, with several interruptions of infliximab until his death 14 months later with severe pancytopenia due to progression of amyloidosis, as shown at autopsy.

Figure 1 Serum C reactive protein (CRP), serum creatinine (Cr(s)), and proteinuria (PU) in our patient after anti‐tumour necrosis factor treatment.

We chose etanercept initially because a case had been reported of a good response of AA amyloidosis to etanercept in 2001² and the results of the clinical trial showing lack of efficacy of etanercept in Crohn's disease had not been published.³ This case illustrates the requirement in secondary amyloidosis for exhaustive control of any inflammatory activity, and highlights the fact that delay in providing effective treatment may prove fatal. Etanercept also lacks effectiveness for preventing reactivation of Crohn's disease. Accordingly, we should always choose infliximab for this type of patient, even if Crohn's disease has been inactive for a long period.

Conflict of interest: declared (the declaration can be viewed on the Gut website at http://www.gutjnl.com/supplemental).