Article Text

PDF
THU0043 Targeted medicine: therapeutic use of functional cytokine assays in complex inflammatory arthritis
  1. EEP Htut1,
  2. L Ceron-Gutierrez2,
  3. R Doffinger2 3,
  4. J Rees1
  1. 1Rheumatology
  2. 2Immunology, Addenbrooke's Hospital
  3. 3National Institute of Health Research, Cambridge Biomedical Research Centre, Cambridge, United Kingdom

Abstract

Background Functional cytokine assays have been limited to experimental models of inflammatory arthritis without translation into clinical therapy.

Objectives To illustrate the successful use of functional cytokine assays in providing targeted treatment for complex inflammatory arthritis.

Methods A 24 year old male presented in 2014 with a florid asymmetrical polyarthritis associated with an elevated acute phase response (ESR 50, CRP 42, ALP 132). He had no history of psoriasis, inflammatory bowel or eye disease and no family history.

Vasculitis and viral arthritis screen, ACE, ANA, Anti dsDNA, RF and CCP were negative. He was positive for HLA B27 without evidence of spondyloarthropathy on imaging. He was noted to have a monoclonal gammopathy of uncertain significance with normal bone profile, unremarkable urinary BJP and whole body CT scan. His joint symptoms responded to corticosteroid therapy with the addition of hydroxychloroquine and methotrexate. In 2015, his clinical condition had significantly deteriorated with worsening joint inflammation, 3 kg weight loss with a sudden rise in acute phase response, without proven infection. His functionality declined with long term sickness from work.

Biochemical tests revealed: Hb 123, MCV 87.2, Plt 393, Neutrophil 7.76, ESR 86, Alb 31, Calcium 2.68, ALP 387 (noted to be of bony origin), CRP 286, Ferritin 1161, PT 13, and APTT 39. Renal function, protein electrophoresis, blood film, haemolytic screen, viral and autoimmune liver screens were unremarkable. Hydroxychloroquine and methotrexate were temporarily with-held at this stage, although he was maintained on prednisolone 20 mg, with a partial response in his joint symptoms. An infiltrative pathology was a concern and was subsequently excluded.

The next therapeutic step would have been an anti-TNF agent. Nevertheless, due to his atypical and complex disease course, cytokine assays were performed to further characterise his disease profile and provide targeted treatment. Results showed an elevated IL6 production; IV Tocilizumab was selected for the treatment of his inflammatory arthritis. He has had a remarkable response in terms of his systemic and joint symptoms as well as considerable biochemical improvement. He was able to de-escalate his corticosteroid regime and return to work.

Results TNF alpha, IL1 beta, and IL-6 are important inflammatory mediators and targets of intervention in the treatment of Rheumatoid arthritis. They may be induced in vivo and in vitro using Toll like receptor mediated innate activation. Active Whole Blood Cytokine Profiling was performed for the patient and compared to healthy controls. Innate activation of whole blood with various TLR agonists including LPS (TLR4), PAM3 (TLR1/2), Imiquimod (TLR7) revealed low induction of TNF alpha and IL1 beta in the patient when compared to controls. In contrast, the patient showed an elevated IL-6 production. Patient's cytokine levels in serum and in non-activated whole blood were normal.

Conclusions Our case highlights the potential progression to personalised medicine in achieving optimal patient outcome delivered in a cost-effective way.

Functional cytokine assays in the appropriate context and within selected patient groups can help to achieve disease remission by allowing targeted treatment.

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.