Rheumatology Advance Access originally published online on December 20, 2005
Rheumatology 2006 45(3):357-359; doi:10.1093/rheumatology/kei264
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LETTER TO THE EDITOR |
Infliximab treatment in a patient with rheumatoid arthritis on haemodialysis
Rheumatology, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
Correspondence to: mhamoudeh{at}hmc.org.qa
SIR, Anti-tumour necrosis factor (TNF) 
has been shown to be very effective in rheumatoid arthritis (RA). Patients with RA with renal failure are difficult to treat. Special attention is required to the possible increase in toxicity and to dose adjustment of the drugs used to treat this disease. We report our experience in treating such a patient with infliximab, a monoclonal TNF antagonist.
A 45-yr-old female university professor presented in April 2002 with a 2-month history of painful and swollen joints of the small joints of both hands, wrists, knees, elbows and shoulders associated with morning stiffness of 2–3 h duration.
In 1984 she was diagnosed with chronic glomerulonephritis of no obvious cause and in 1985 she had cadaveric renal transplant. The transplanted kidney was removed in 1995 because of chronic rejection and since then she has been on regular haemodialysis. In 1996 she was found to have hepatitis C, with a positive polymerase chain reaction (PCR) test, and was treated with interferon for 6 months. The PCR test became negative at the end of 6 months of therapy. One year later the liver enzymes increased again and the hepatitis C PCR test became positive at a high titre. She was again given interferon for 1 yr, which normalized the liver enzymes. Liver biopsy done in 1999 showed changes of very early fibrosis only. The patient has severe allergic reaction to sulpha drugs in childhood and had had marked hypertrichosis during treatment with cyclosporin associated with her kidney transplant.
Physical examination showed very tender and swollen MCPs, PIPs, wrists, elbows, knees and shoulders. Laboratory investigations revealed positivity for rheumatoid factor of 320 IU, CRP 96 mg/dl, ANA 1:160, and negativity for anti-double-stranded DNA antibodies. Her ESR was 105 mm/h and haemoglobin was 9.7 gm/dl.
She was treated with small doses of steroids and non-steroidal anti-inflammatory drugs (NSAIDs) but the response was inadequate. She frequently required joint aspiration and local steroid injection in different joints. She was tested for anti-cyclic citrullinated peptides in April 2004 and was positive, at more than 100 U. In May 2004 she presented with an acute flare, with very painful, swollen joints of the hands, both wrists, shoulders and the knees. Her ESR was 93 mm/h and CRP was 96 mg/l. The use of infliximab was discussed with the patient and this drug was given at 3 mg/kg at 0, 2 and 6 weeks, and then every 8 weeks. The arthritis improved remarkably with dramatic reduction of pain, swelling and improvement of the functional status. After the initial two infusions she developed post-infusion transient itching that responded to cetirizine 10 mg daily.
When she was seen in December 2004 she had no significant stiffness but still had mild swelling of the both knees with little pain. Her ESR was 34 mm/h and CRP was 28 mg/dl. She was maintained on infliximab infusions every 8 weeks.
The literature contains little information on the treatment of RA in patients with end-stage renal failure who are on haemodialysis. The potential toxicity of the drugs used, such as NSAIDs and disease-modifying drugs, deserves special attention.
NSAIDs expose dialysis patients to an increased risk of gastroduodenal ulceration and bleeding, and it is advised that their use should be limited to short courses [1].
Methotrexate, which is the most commonly used drug and one of the most effective drugs in RA, is cleared primarily by the kidney and has been associated with life-threatening complications in a patient on haemodialysis who was on a small dose [2].
Azathioprine may be used but the dose should be reduced by 50% if the glomerular filtration rate is less than 10% [3]. In haemodialysis the drug was found to be effectively eliminated, suggesting that the dose of azathioprine can be maintained if the patient is on haemodialysis [4].
The hydroxychloroquine dose should be reduced by 50% in renal impairment [3]. Renal failure predisposes to a higher incidence of myopathy, neuropathy and cardiac myotoxicity in patients on hydroxychloroquine [5].
Cyclosporin may be given to patients with renal impairment on haemodialysis, at the same dose for patients with normal renal function [3]. A patient with bone marrow aplasia during haemodialysis was reported to improve after treatment with cyclosporin while he was on dialysis [6].
Leflunomide may be used in patients on haemodialysis and reduction of the dose does not appear to be required [7].
There are no reports or standards for the use of sulphasalazine in haemodialysis patients. However, Akiyama et al. reported the pharmacokinetics of this drug in a gastrectomized patient on haemodialysis who also had amyloidosis, and found that the drug metabolites did not differ from those in healthy controls during the 5 days after drug administration [8].
Anti TNF- is a new category of drug used in the treatment of RA, but very little is known about its use in renal impairment or in haemodialysis. The three available TNF antagonist are etanercept, infliximab and adalimumab. Infliximab is a chimeric monoclonal antibody composed of the human constant region and murine variable region.
Singh et al. reported a patient with RA who failed to respond to treatment with several DMARDs and responded well to infliximab [9]. Yee et al. reported the use of infliximab in complicated sarcoidosis in a patient who required haemodialysis during the course of the disease [10]. Although the patient's symptoms improved, the clinical course was complicated by the development of a hypercoagulable state, which improved after discontinuation of infliximab therapy. Ortiz-Santamaria et al. [11] reported the use of infliximab in six patients with amyloidosis (related to RA in five cases and to ankylosing spondylitis in one). Two of the six patients were on haemodialysis; one developed transient pancytopenia concurrently with renal function impairment and the infliximab was withdrawn. The other patient did not have any adverse event but the 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.
Searching the literature, we could not find any other reported cases of the use of other antagonists in rheumatoid patients with renal failure on haemodialysis.
Our patient, like the patient of Singh et al., responded very well to treatment with infliximab and was able to return to her activities. She tolerated the drug well and did not show any unusual side-effects, which suggests that patients on haemodialysis can tolerate this drug and that the drug maintains its efficacy.
The exact pharmacokinetics of infliximab in patients on dialysis are not known. However, in patients with normal renal function, infliximab has the lowest volume of distribution among the available TNF antagonists, which indicates that the distribution of infliximab outside the blood circulation and the inflamed tissue is limited [12].
Our case and the case of Singh et al. demonstrate the potential use of infliximab and possibly other anti-TNF biologicals in the treatment of rheumatoid patients with end-stage renal failure on haemodialysis.
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The author has declared no conflicts of interest.
References
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- Boulanger H, Launay-Vacher V, Hierniaux P, Fau JB, Deray G. Severe methotrexate intoxication in a hemodialysis patient treated for rheumatoid arthritis. Nephrol Dial Transplant 2001;16:1087.
[Free Full Text] - Aronoff GR, Brier M. Prescribing drugs in renal disease. In: Brenner BM, ed. Brenner and Rector's The Kidney, Vol. 2. 7th edn. Philadelphia: Saunders, 2004:2850–70.
- Schusziarra V, Ziekursch V, Schlamp R, Siemensen HC. Pharmacokinetics of azathioprine under hemodialysis. Int J Clin Pharmacol Biopharm 1976;14:298–302.[Medline]
- Stein M, Bell MJ, Ang LC. Hydroxychloroquine neuromyotoxicity. J Rheumatol 2000;27:2927–31.[Web of Science][Medline]
- Vega J, Rodriguez M de L, Vasquez A, Torres C. Bone marrow aplasia during hemodialysis successfully treated with cyclosporin. Report of one case. Rev Med Chil 2004;132:989–94.[Medline]
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[Abstract/Free Full Text] - Yee AM, Pochapin MB. Treatment of sarcoidosis with infliximab anti-tumor necrosis factor-alpha therapy. Ann Intern Med 2001;135:27–31.
[Abstract/Free Full Text] - Ortiz-Santamaria V, Valls-Roc M, Sanmari M, Olive A. Anti-TNF treatment in secondary amyloidosis. Rheumatology 2003;42:1425–6.
[Free Full Text] - Nestrov I. Clinical pharmacokinetics of tumor necrosis factor antagonists. J Rheumatol 2005;74:13–8.
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