Rheumatology Advance Access originally published online on July 11, 2006
Rheumatology 2006 45(10):1314-1315; doi:10.1093/rheumatology/kel211
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Effective co-administration of infliximab and etanercept following the failure of sequential anti-TNF agents in a patient with HLA-B27-associated arthropathy
Department of Rheumatology, Connolly Hospital, Blanchardstown, Dublin 15, Ireland
Correspondence to: M. Barry. E-mail: mbarry{at}ireland.com
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Introduction |
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SIR, We report the successful use of a combination of anti-TNF-
agents in a man with refractory human leucocyte antigen (HLA)-B27-associated arthritis. A 28-yr-old man presented in 1999 with an 8-month history of left knee pain and swelling, associated with left hip and wrist pain. Erythrocyte sedimentation rate (ESR) was 57 mm/h, rheumatoid and anti-nuclear factors were negative. He was HLA-B27 positive. The left knee was aspirated; fluid analysis was negative for organisms and crystals; TB culture was negative. Lyme, brucella, HIV and hepatitis serology was negative, as were stool and urine cultures. HLA-B27-associated inflammatory arthritis was diagnosed. By 2001, he had developed synovitis of three distal interphalangeal joints, left wrist and knee despite salazopyrin and subsequently methotrexate (MTX) 20 mg/week. There was a marked persistent acute phase response (Fig. 1). In March 2001, infliximab 3 mg/kg with MTX 20 mg/week resulted in a partial response for 6 weeks. This could not be maintained despite increasing both the dose and the frequency. In January 2002, he received two intra-articular injections of 100 mg of infliximab to the left knee, a procedure described in the literature [1], but which produced no sustained improvement. There was no benefit from leflunomide 20 mg, subsequent combination of anakinra and MTX 20 mg/week or surgical synovectomy of the left knee in September 2003.
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By October 2003, he had developed marked synovitis of the right knee and ankle. Adalimumab 40 mg every 2 weeks, with oral MTX 20 mg/week, resulted in a partial clinical response for 8 weeks though ESR never fell below 69 mm/h.
Etanercept 25 mg twice a week with subcutaneous MTX 20 mg/week, commenced in January 2004, was ineffective. In June 2004, a single infusion of rituximab with subcutaneous MTX and tapering high dose oral steroid were similarly ineffective. The combination of doxycycline 100 mg/day and myocrisin 50 mg/week intramuscularly was latterly unsuccessful.
By May 2005, he had persistent marked synovitis of the left wrist, knees, ankles and metatarsophalangeal joints and had developed spinal symptoms. The ESR remained markedly elevated with persistent thrombocytosis. Rheumatoid and anti-nuclear factors remained negative.
As his disease had proved refractory to conventional disease-modifying and individual biological therapies, it was decided to offer him a combination of anti-TNF- agents. In June 2005 he was commenced on infliximab 5 mg/kg every 8 weeks and etanercept 25 mg twice a week, with cotrimoxazole prophylaxis for Pneumocystis carinii pneumonia (PCP). MTX was not restarted due to potential interaction with cotrimoxazole.
Within weeks of commencing this combination, there was a dramatic improvement in the affected joints. ESR and platelet count fell rapidly to normal levels for the first time since 1999. His condition has been in remission for 6 months. Prednisolone is being weaned. He has not suffered any infectious or other complications to date.
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Discussion |
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This patient had HLA-B27-associated arthropathy refractory to many treatments over a 6 yr period. He received five traditional disease modifying agents and was treated with five biologic agents [three anti-TNF-
, one interleukin (IL)-1 receptor antagonist and a B-cell anti-CD20 agent], all in combination with MTX. Further options were limited. Consideration was given to using cyclophosphamide and also to stem-cell transplantation despite potential major morbidities associated with both. We felt that a trial of combination anti-TNF agents should be used first despite the failure of the individual agents together with MTX. There are reasons why such a combination might lead to enhanced TNF neutralization. The agents have different modes of action [2, 3]. It is known that infliximab binds active and inactive soluble TNF-, while etanercept only binds the active form. The binding of infliximab to membrane-associated TNF- can cause cell lysis. Etanercept alone binds and neutralizes lymphotoxin. Anti-TNF agents also affect osteoprotegerin and receptor activator of NF-B ligand [4, 5] and may have effects on synovial inflammation as yet undescribed. It is well recognized that some patients will respond to one TNF agent but not to another [6, 7], and genetic polymorphisms influencing response are being identified [8, 9]. It makes intuitive sense therefore that combining anti-TNF agents might have additive benefits. With regard to potential toxicity, both infliximab and etanercept as single agents have a good safety profile, provided that appropriate measures have been taken regarding screening for tuberculosis and precautions have been taken against other infections. We prescribed cotrimoxazole for PCP prophylaxis, perhaps influenced by personal experience of PCP associated with infliximab [10].
We intend to reduce the dose of infliximab at 1 yr to 3 mg/kg 8 weekly. If successful, the cost of combination therapy would be similar to that of Infliximab as a single agent at a dose of 5 mg/kg.
We have not found other cases describing the simultaneous use of anti-TNF agents. In this individual, the combination was highly effective following the failure of the agents used individually with MTX. For those patients with inflammatory arthritis who do not respond to individual anti-TNF agents, the possibility of using a combination of therapies merits further investigation.
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The authors would like to thank Prof. John Isaacs (University of Newcastle-upon-Tyne) for his helpful comments during the preparation of this case report.
C.S. is in receipt of an unrestricted research grant from Wyeth Pharmaceuticals. The other authors have declared no conflict of interest.
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References |
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- Nikas SN, Temekonidis TI, Zikou AK, Argyropoulou MI, Efremidis S, Drosos AA. (2004) Treatment of resistant rheumatoid arthritis by intra-articular infliximab injections: a pilot study. Ann Rheum Dis 63:102–3.
[Free Full Text] - Scallon B, Cai A, Solowski N, et al. (2002) Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther 301:418–26.
[Abstract/Free Full Text] - Mpofu S, Fatima F, Moots RJ. (2005) Anti-TNF-alpha therapies: they are all the same (aren't they?). Rheumatology 44:271–3.
[Free Full Text] - Catrina AI, af Klint E, Ernestam S, et al. (2006) Anti-tumor necrosis factor therapy increases synovial osteoprotegerin expression in rheumatoid arthritis. Arthritis Rheum 54:76–81.[CrossRef][Web of Science][Medline]
- Zwerina J, Hayer S, Tohidast-Akrad M, et al. (2004) Single and combined inhibition of tumor necrosis factor, interleukin-1, and RANKL pathways in tumor necrosis factor-induced arthritis: effects on synovial inflammation, bone erosion, and cartilage destruction. Arthritis Rheum 50:277–90.[CrossRef][Web of Science][Medline]
- van Vollenhoven R, Harju A, Brannemark S, Klareskog L. (2003) Treatment with infliximab (Remicade) when etanercept (Enbrel) has failed or vice versa: data from the STURE registry showing that switching tumour necrosis factor alpha blockers can make sense. Ann Rheum Dis 62:1195–8.
[Abstract/Free Full Text] - Cohen G, Courvoisier N, Cohen JD, Zaltni S, Sany J, Combe B. (2005) The efficiency of switching from infliximab to etanercept and vice-versa in patients with rheumatoid arthritis. Clin Exp Rheumatol 23:795–800.[Web of Science][Medline]
- Padyukov L, Lampa J, Heimburger M, et al. (2003) Genetic markers for the efficacy of tumour necrosis factor blocking therapy in rheumatoid arthritis. Ann Rheum Dis 62:526–9.
[Abstract/Free Full Text] - Tutuncu Z, Kavanaugh A, Zvaifler N, Corr M, Deutsch R, Boyle D. (2005) Fcgamma receptor type IIIA polymorphisms influence treatment outcomes in patients with inflammatory arthritis treated with tumor necrosis factor alpha-blocking agents. Arthritis Rheum 52:2693–6.[CrossRef][Web of Science][Medline]
- Tai TL, O'Rourke KP, McWeeney M, Burke CM, Sheehan K, Barry M. (2002) Pneumocystis carinii pneumonia following a second infusion of infliximab. Rheumatology 41:951–2.
[Free Full Text]
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