1. Faculty of Medicine and Health
  2. School of Medicine
  3. Research groups
  4. Inflammatory Musculoskeletal

Inflammatory Musculoskeletal

  • Group summary: The unit has the principle of accurate phenotyping to predict prognosis through all stages of disease. The ultimate ambition is prevention of disease. The work is based on a nationwide network of primary care referrals. Arthritis prevention centres are being developed. Several stratified intervention studies have been undertaken.

What we do

The group focuses on inflammatory arthritis throughout its continuum; from at risk individuals, to pre-clinical disease through to remission or resistance. At each defined stage of the continuum patients are phenotyped using clinical, imaging and immunological biomarkers.  This allows an accurate prognostic index to be developed, predicting outcome and allowing targeted therapy for these individuals.  The key stages of the continuum are as follows:

  1. At risk individuals – these individuals are are identified by family history or bythe presence of ACPA (anti-CCP). Particular attention is focused on initiation of autoimmunity in these individuals, for example we have shown for the first time that this population has increased periodontal disease, with increased colonisation with p.ginivalis.

    Clinical imaging and immunological biomarkers are used to produce a risk score predicting riskof progression to clinical disease. Intervention studies are being undertaken, stratified for risk of progression.

    We have shown that the first musculoskeletal involvement is often non-synovitic,  a unique interosseous peritendinitis having been identified.  In palindromic rheumatism, we have demonstrated patients flare in a predominately extra articular location and the inflammation largely resolves with improvement in clinical condition.
     
  2. At presentation – RA patients are tested for their T-cell subsets as numerical abnormalities of these predict methotrexate response.  These patients are then stratified for intervention for more aggressive therapy if poor outcome is predicted.  Psoriatic arthritis inception cohort study – patients with inflammatory back symptoms are part of the SPARRO programme for psoriatic arthritis patients.
     
  3. Remission – with aggressive therapy, larger numbers of patients are achieving remission . A key focus has been producingthe evidence base to logically manage these patients.  Patients in remission have their T-cell subsets enumerated, and together with imaging characteristics have been shown to predict the likelihood of successful tapering therapy.
     
  4. Resistant patients – defined as those who have  failed both csDMARDs and bDMARDs have been identified.  The mechanism by which this occurs is being investigated. The VEDERA study has been investigating whether early use of anti-TNF can prevent resistance to subsequent drug therapy linked to the development of epigenetic changes.
     
  5. A particular interest has been the imaging of muscle disease, in these disorders, using shear wave elastography and MRI; developing new imaging sequences to improve diagnosis and outcome.
     
  6. Another area of research interest is B-cell depletion identifying association between response and depletion and determinig the timing of retreatment/titrating the dose.

Funding

Key publications

Key publications our team has contributed to

  1. Mankia K, Emery P.  Is localised autoimmunity the trigger for rheumatoid arthritis? Unravelling new targets for prevention. Discov Med 2015; 20:129-35.
     
  2. Mankia K, Emery P. Decoding Palindromic rheumatism. Arthritis Digest 2015; 6:25.
     
  3. Mankia K, Emery P. Anti-Porphyromonas gingivalis antibodies in rheumatoid arthritis: Comment on the article by Seror et al. Arthritis Rheumatol 2015; 67: 3329-30.
     
  4. Mankia K, Emery P.  Preclinical Rheumatoid Arthritis: Progress towards Prevention. Arthritis Rheumatol 2016; 68:779-88.
     
  5. Mankia K, Emery P. A new window of opportunity in rheumatoid arthritis: targeting at-risk individuals. Curr Opin Rheumatol 2016; 28:260-6.
     
  6. Mankia K, Nam J, Emery P. Identifying Arthralgia Suspicious for Progression to Rheumatoid Arthritis: Comment on the article by Steenbergen et al. Ann Rheum Dis 2017; 76; e14.
     
  7. Mankia K, Emery P. Imminent rheumatoid arthritis can be identified in primary care. Ann Rheum Dis 2017; 76:e42.
     
  8. Pentony P, Duquenne L, Dutton, K, Mankia K, Gul H, Vital E, Emery P. The initiation of autoimmunity at epithelial surfaces: a focus on Rheumatoid Arthritis and Systemic Lupus Erythematosus. Discov Med 2017; 24(133): 191-200.
     
  9. Cheng Z, Meade J, Mankia K, Emery P, Devine DA. Periodontal disease and periodontal bacteria as triggers for rheumatoid arthritis. Best Pract Res Clin Rheumatol 2017; 31(1):19-30.
     
  10. Emery P, Mankia K, Nam JL. Individuals at risk of rheumatoid arthritis – The evolving story. Best Pract Res Clin Rheumatol 2017; 31(1):1-2.
     
  11. Mankia K, Emery P. What can palindromic rheumatism tell us? Best Pract Res Clin Rheumatol 2017; 31(1):90-98.
     
  12. Mankia K, D’Agostino MA, Wakefield R, Nam J, Mahmood W, Grainger A, Emery P. Identification of a distinct imaging phenotype may improve the management of palindromic rheumatism. Annals of the Rheumatic Diseases 2018 [Epub].
     
  13. Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, Singh A, Pedersen RD, Koenig A, Freundlich B. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early , moderate to severe, rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial.  Lancet. 2008;372:375-82.
     
  14. Anis A, Zhang W, Emery P, Sun H, Singh A, Freundlich B, Sato R.  The effect of etanercept on work productivity in patients with early active RA: Results from the COMET study.  Rheumatology  (Oxford). 2009;48:1283-9.
     
  15. Kekow J, Moots RJ, Emery P, Durez P, Koenig A, Singh A, Pederson R, Robertson D, Freundlich B, Sato R.  Patient-reported outcomes improve with etanercept plus methotrexate in active early rheumatoid arthritis and the improvement is strongly associated with remission:  The COMET trial.   Ann Rheum Dis. 2010;69:222-25.
     
  16. Emery P, Tore K, Combe B, Freundlich B, Robertson D, Ferdousi T, Bananis E, Pedersen R, Koenig A. Combination etanercept and methotrexate provides better disease control in very early (>4 months) versus early rheumatoid arthritis (>4 months and <2 years): post hoc analyses from the COMET study. Ann Rheum Dis. 2012;71:989-92.
     
  17. Emery P, Hammoudeh M, FitzGerald O, Combe B, Martin-Mola E, Buch MH, Krogulec M, Williams T, Gaylord S, Pedersen R, Bukowski  J, Vlahos B. Sustained remission with etanercept tapering in early rheumatoid arthritis (PRIZE). N Engl J Med 2014;371: 1781 – 92.
     
  18. Vital EM, Wittmann M, Edward S, Yusof MYM, MacIver H, Pease CT, Goodfield M, Emery P.Brief report: responses to rituximab suggest B cell-independent inflammation in cutaneous systemic lupus erythematosus. Arthritis Rheumatol 2015;67:1596-91.
     
  19. Vital EM, Dass S, Buch MH, Rawstron AC, Emery P. An extra dose of rituximab improves clinical response in rheumatoid arthritis patients with initial incomplete B Cell depletion: a randomised controlled trial. Ann Rheum Dis. 2015;74:1195-1201.
     
  20. Yusof MYM, Vital EM, Das S, Dass S, Arumugakani G, Savic S, Rawstron AC, Emery P.  Repeat cycles of rituximab on clinical relapse in ANCA-associated vasculitis: identifying B cell biomarkers for relapse to guide retreatment decisions. Ann Rheum Dis 2015; 9:1734-8.
     
  21. Md Yusof MY, Shaw D, El-Sherbiny YM, Dunn E, Rawstron AC, Emery P, Vital EM. Predicting and managing primary and secondary non-response to rituximab using B-cell biomarkers in systemic lupus erythematosus. Ann Rheum Dis 2017; 76:1829-1836.
     
  22. Yusof MYM, Kabia A, Darby M, Lettieri G, Beirne P, Vital EM, Dass S, Emery P. Effect of rituximab on the progression of rheumatoid arthritis-related interstitial lung disease: 10 years’ experience at a single centre. Rheumatology 2017; 56:1348-1357

Who we are

People

Professor Paul Emery

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