Rheumatology Advance Access originally published online on October 29, 2007
Rheumatology 2007 46(12):1865-1866; doi:10.1093/rheumatology/kem231
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Comment on: Failure of anti-TNF therapy in TNF Receptor 1-Associated Periodic Syndrome (TRAPS)
Clinical Immunology Unit, Nottingham University Hospitals UK
Correspondence to: E. Drewe, Clinical Immunology Unit, Nottingham University Hospital, QMC Campus, Derby Road, Nottingham, NG7 2UH, UK. E-mail: liz.drewe{at}nottingham.ac.uk
SIR, Jacobelli's [1] letter entitled ‘Failure of anti-TNF therapy in TNF Receptor 1-Associated Periodic Syndrome (TRAPS)’ referred to our prospective study of etanercept in TRAPS [2]. The 5-yr follow-up on these five subjects with C33Y TRAPS and our experience with a further four such patients treated with etanercept will assist this discussion. Our experience with adalimumab in 2/5 of these initial TRAPS patients and possible benefit of moxifloxacin in a single patient is also described.
Patient 1 was a 48-yr-old man with severe lifelong TRAPS [2]; despite initial good response to etanercept, the decline in response to etanercept that was seen in cycle 2 of treatment continued post-study so etanercept was withdrawn. Subsequently two doses of intravenous infliximab at 5 mg/kg produced a paradoxical inflammatory reaction similar to Jacobelli's description [1]. In 2003, he received a 16-week course of the fully human recombinant anti-tumour necrosis factor (TNF) monoclonal antibody adalimumab which has proven benefits in RA [3]. Adalimumab 40 mg subcutaneously was commenced on a background of fevers, myalgia and abdominal pain. During the first week of therapy symptoms persisted but after 2 weeks of treatment a severe attack occurred requiring intravenous methylprednisolone. Dose increase to 40 mg adalimumab twice weekly coincided with further severe attack. Median CRP and ESR levels were significantly higher on adalimumab compared with the 16-week pre-treatment baseline. Total oral prednisolone dose was similar in the two 16-week periods but 3000 mg i.v. methylprednisolone was given on adalimumab compared with 1000 mg during baseline. Treatment for this subject has remained challenging accompanied by side-effects of long-term corticosteroid treatment, namely cataracts, obesity and osteoporosis.
Interim follow-up on patient 2, 25-yr-old female with renal amyloidosis in the initial study, has previously been described in this journal [4]. This subject had good sustained response to etanercept but poor compliance was associated with relapse of nephrotic syndrome with end-stage renal failure. In 2005, she underwent successful live related renal transplant. Etanercept was continued to limit the development of graft amyloidosis but it has recently been withdrawn to allow conception.
Patient 3, a 55-yr-old man with frequent abdominal attacks in the initial study, has had continued sustained benefit from etanercept. He is virtually asymptomatic on treatment but has repeatedly developed abdominal attacks within 2 weeks of stopping etanercept. In 2003, this patient had a trial of adalimumab. Prior to treatment, he had abdominal attacks every 4–6 weeks. A flare of TRAPS occurred with the first dose of 40 mg adalimumab and initial treatment with oral prednisolone failed to reduce symptoms. After 2 weeks of continued adalimumab, a severe attack with 41°C fever, abdominal pain, diarrhoea and vomiting required his first dose of methylprednisolone for 5 yrs. CRP levels were 386 mg/l; the highest level recorded for over 3 yrs, with ESR 81 mm/h. Treatment with adalimumab was stopped at 3 weeks but symptoms of fatigue, weakness and intermittent abdominal pain persisted over 2 months with 3 kg weight loss.
Patient 4, a 33-yr-old female, had clinical but not laboratory evidence of response to etanercept. She continued etanercept post-study for a further 2 yrs but developed recurrent Streptococcus pneumoniae chest infections despite good pneumococcal antibody levels following Pneumovax II. Intolerances to several antibiotics led to moxifloxacin 400 mg daily being introduced in 2004. Improvement in her chest symptoms was accompanied by dramatic improvements in her TRAPS and has not required corticosteroids to date, but CRP and ESR have remained elevated. During periods of missing 2 or 3 days of moxifloxacin she describes her ‘TRAPS’ symptoms as returning. She has declined a formal trial of withdrawal of this drug.
Patient 5 was a 31-yr-old female described continued benefit with etanercept post-study. However, she noted recurrent upper respiratory tract infections on etanercept, and hence stopped etanercept.
Four further patients have subsequently received etanercept for C33Y TRAPS in our unit. One of these, a 54-yr-old man with renal amyloidosis, has been described [3]. Initial good response to etanercept was not sustained and he is on haemodialysis, with severe pancytopaenia-necessitated withdrawal of etanercept that resolved on stopping. Of the three further patients, one has had excellent sustained response to etanercept, one had partial response but developed abnormal liver function tests and the remaining patient has made initial good response, but longer term evaluation is required.
Following the observation that patient 4's TRAPS improved whilst taking moxifloxacin, three C33Y TRAPS subjects received moxifloxacin for 1 month and one of these also received ciprofloxacin without benefit.
We conclude that etanercept does have certain benefits for TRAPS patients but it varies and may not be sustained. We agree that infliximab may cause paradoxical inflammatory attacks and add that adalimumab may also have this effect. The response of patient 4 to moxifloxacin is of interest and whether this could relate to suppression of a bacterial trigger or anti-inflammatory effects of the antibiotic, e.g. MAP kinase and NF-
B, is unknown [5].
Disclosure statement: The authors have declared no conflicts of interest.
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- Jacobelli S, Andre M, Alexandra J-F, Dode C, Papo T. Failure of anti-TNF therapy in TNF receptor 1-associated periodic syndrome. Rheumatology (2007) 46:1211–2.
[Free Full Text] - Drewe E, McDermott EM, Powell PT, Isaacs JD, Powell RJ. Prospective study of anti-tumour necrosis factor receptor superfamily 1B fusion protein, and case study of anti-tumour necrosis factor receptor associated periodic syndrome (TRAPS). Rheumatology (2003) 42:235–9.
[Abstract/Free Full Text] - Keystone EC, Kavanaugh AF, Sharp JT, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomised, placebo controlled, 52 weeks trial. Arthritis Rheum (2004) 50:1400–11.[CrossRef][Web of Science][Medline]
- Drewe E, Huggins ML, Morgan AG, Cassidy MJD, Powell RJ. Treatment of renal amyloidosis with etanercept in tumour necrosis factor receptor-associated periodic syndrome. Rheumatology (2004) 43:1405–8.
[Abstract/Free Full Text] - Weiss T, Shalit I, Blau H, et al. Anti-inflammatory effects of moxifloxacin on activated human monocytic cells: inhibition of NF-B and mitogen-activated protein kinase activation and of synthesis of proinflammatory cytokines. Antimicrob Agents Chemother (2004) 48:1974–82.
[Abstract/Free Full Text]
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