Experiences on the use of biological drugs in psoriatic arthritis-associated amyloidosis

Amyloid A (AA) amyloidosis is a severe complication of inflammatory rheumatic diseases, mainly seen in rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS), and is associated with increased mortality (1, 2). However, with regard to psoriatic arthritis (PsA), the association is with amyloidosis weak and the published data are based mainly on case reports (3). A review by Kagan et al found 39 cases with psoriasis-associated amyloidosis reported by 1998, and 85% of these cases had a concomitant arthropathy (3). To achieve an early diagnosis of amyloidosis, the use of abdominal subcutaneous fat aspiration (ASFA) biopsy has been recommended in the care of RA patients whenever there is a continuously active disease. However, in cases of PsA, the diagnosis of amyloidosis often seems to be delayed to the stage of renal disorder (3); this may be explained partly by the rarity of this manifestation in PsA. In recent years there have been some case reports of active drug treatment of this manifestation (3–5), but with varying results. To gain a better knowledge of the outcome of PsAassociated amyloidosis, we examined a large biopsy file for amyloidosis associated with rheumatic diseases (RA, AS, JIA, and PsA) in more than 2600 patients from 1987 to 2000 at the Rheumatism Foundation Hospital (RFH), a nationwide secondary centre for rheumatic diseases in Finland, to find cases with PsA-associated amyloidosis. The biopsy indications were suspicion of amyloidosis due to continuously active inflammation [high C-reactive protein (CRP)] or clinical signs of amyloidosis, such as proteinuria and/or renal insufficiency. The biopsy file revealed 70 patients with a clinical diagnosis of PsA analysed by Congo red staining of ASFA specimens to show amyloids. The medical records of the patients were reviewed. Forty-one (59%) of the 70 patients met the Caspar criteria for PsA (6), including three cases with a positive biopsy for amyloids; two of these cases were treated with biologicals and are reported here in a more detail. To assess renal function we used the Cockcroft–Gault formula (7). One of the patients had oligoarthritis in childhood. After 20 years she developed a psoriatic rash and active polyarthritis simultaneously. Her disease was resistant to disease-modifying anti-rheumatic drugs (DMARDs), and amyloidosis was documented by ASFA biopsy 8 years later. At this stage she had no signs of renal disorder, that is she had normal renal function and no proteinuria. Despite the use of methotrexate (MTX) and low-dose prednisolone, her renal function deteriorated and she was treated with etanercept. However, her renal function was not stabilized until the treatment was changed to tocilizumab (Table 1). The other patient with active psoriatic spondyloarthropathy also had subclinical amyloidosis. Her disease did not respond to MTX and low-dose prednisolone. Biological therapy with adalimumab was started at a phase when she had moderate renal failure. Later she developed proteinuria but her renal function stabilized. Her treatment was carried out with etanercept for a short period due to suspicion of side-effects of adalimumab. However, adalimumab was later used without problems (Table 1). Including our patients, there are now seven reported cases of PsA-associated amyloidosis that have been treated with anti-tumour necrosis factor (TNF)a therapy (Table 1). Except for inefficacy in one of our cases and one infection-related death reported (5), the therapy seems to have been beneficial in the rest of the patients. Overall, our results in PsA support the published data on the efficacy of anti-TNFa therapy in other rheumatic conditions associated with amyloidosis (5). On the basis of case reports, the efficacy of tocilizumab on RAand JIA-associated amyloidosis seems promising (9, 10). Our experience shows that tocilizumab may be a good alternative for those PsA patients with amyloidosis whose disease is resistant to DMARDs or anti-TNFa therapy. Michael Schirmer, Department of Internal Medicine I, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. E-mail: michael.schirmer@i-med.ac. at