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Management der Polymyalgia rheumatica und der Großgefäßvaskulitiden

Management of polymyalgia rheumatica and large vessel vasculitis

  • Schwerpunkt: Management rheumatischer Erkrankungen
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Zusammenfassung

Bildgebende Verfahren wie die Gelenk- und Farbduplexsonographie, die Magnetresonanztomographie und Positronenemissionstomographie erleichtern heute die Diagnose sowohl der Polymyalgia rheumatica (PMR) als auch der Großgefäßvaskulitiden und haben Einzug in neue Klassifikationskriterien gefunden. So kann bei typischer Klinik einer Arteriitis temporalis und bei passendem Befund in der Farbduplexsonographie (Halozeichen) auf eine Biopsie der A. temporalis verzichtet werden. Der Stellenwert der Methoden für die Beurteilung der Prognose und Krankheitsaktivität im Verlauf ist jedoch unklar. Die PMR wird mit Glukokortikoiden (GC) in einer Initialdosis von bis zu 20 mg/Tag behandelt. Bei den Großgefäßvaskulitiden sind höhere GC-Dosierungen zur Remissionsinduktion erforderlich. Da im Vergleich zur PMR bei der Riesenzellarteriitis (RZA) und der Takayasu-Arteriitis (TA) auch das Rezidivrisiko höher ist und häufiger GC-assoziierte Nebenwirkungen auftreten, wird bei den Großgefäßvaskulitiden primär zusätzlich eine GC-einsparende Therapie mit Methotrexat oder anderen mittelpotenten Immunsuppressiva empfohlen. Neuere Studiendaten lassen zudem eine Wirksamkeit von Biologika erkennen. Ergebnisse erster placebokontrollierter Proof-of-concept-Studien zeigen, dass der Interleukin-6-Rezeptor-Antagonist Tocilizumab sowohl bei Patienten mit RZA als auch bei der PMR den GC-Bedarf reduziert und das Rezidivrisiko senkt. Ustekinumab, ein monoklonaler Antikörper gegen Interleukin-12/23p40, sowie das CTLA-4-Immunglobulin Abatacept haben sich in ersten Pilotstudien bei refraktärer RZA als potenziell wirksam erwiesen. Tumor-Nekrose-Faktor-α-Antikörper waren bei der PMR und RZA in placebokontrollierten Studien ineffektiv, ließen aber in offenen Studien eine Wirksamkeit bei refraktärer TA erkennen.

Abstract

Imaging methods, such as joint and color duplex sonography, magnetic resonance imaging (MRI) and positron emission tomography (PET) nowadays facilitate the diagnosis of polymyalgia rheumatica and large vessel vasculitides and have now been included in the new classification criteria. In patients with typical symptoms, color duplex sonography of the temporal artery can replace a biopsy of the temporal artery for the diagnosis of giant cell arteritis (GCA); however, the role of these methods for patient follow-up and assessment of prognosis is unclear. Polymyalgia rheumatica is treated with glucocorticoids (GC) in an initial dosage of up to 20 mg per day. In patients with large vessel vasculitis higher doses are needed for induction of remission. Furthermore, the rate of relapse and GC-related adverse events are higher in GCA and Takayasu arteritis (TA). Thus, initial GC-sparing treatment with methotrexate or other immunosuppressants is recommended. Recent study data show an effectiveness of biologics. Recent data of the first placebo-controlled proof of concept trials showed that the interleukin-6 antagonist tocilizumab reduces GC requirements and relapse rates in patients with GCA and polymyalgia rheumatica. Both ustekinumab, a monocalonal antibody against interleukin-12/23p40 and the CTLA-4 immunoglobulin abatacept appeared to be effective in recent pilot trials for GCA. Antibodies against tumor necrosis factor alpha (TNF alpha) were ineffective for polymyalgia rheumatica and GCA in placebo-controlled trials but data from open label studies suggested some efficacy in refractory TA.

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Literatur

  1. Adizie T, Christidis D, Dharmapaliah C et al (2012) Efficacy and tolerability of leflunomide in difficult-to-treat polymyalgia rheumatica and giant cell arteritis: a case series. Int J Clin Pract 66:906–909

    Article  CAS  PubMed  Google Scholar 

  2. Alba MA, Garcia-Martinez A, Prieto-Gonzalez S et al (2014) Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients. Medicine (Baltimore) 93:194–201

    Article  Google Scholar 

  3. Bienvenu B, Ly KH, Lambert M et al (2016) Management of giant cell arteritis: recommendations of the French Study Group for Large Vessel Vasculitis (GEFA). Rev Med Interne 37:154–165

    Article  CAS  PubMed  Google Scholar 

  4. Blockmans D, Coudyzer W, Vanderschueren S et al (2008) Relationship between fluorodeoxyglucose uptake in the large vessels and late aortic diameter in giant cell arteritis. Rheumatology (Oxford) 47(8):1179–1184. doi:10.1093/rheumatology/ken119

    Article  CAS  Google Scholar 

  5. Clifford A, Hoffman GS (2014) Recent advances in the medical management of Takayasu arteritis: an update on use of biologic therapies. Curr Opin Rheumatol 26:7–15

    Article  CAS  PubMed  Google Scholar 

  6. Conway R, O’Neill L, O’Flynn E et al (2016) Ustekinumab for the treatment of refractory giant cell arteritis. Ann Rheum Dis 75(8):1578–1579. doi:10.1136/annrheumdis-2016-209351

    Article  PubMed  Google Scholar 

  7. Dasgupta B, Borg FA, Hassan N et al (2010) BSR and BHPR guidelines for the management of giant cell arteritis. Rheumatology (Oxford) 49:1594–1597

    Article  Google Scholar 

  8. Dasgupta B, Cimmino MA, Maradit-Kremers H et al (2012) 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis 71:484–492

    Article  PubMed  PubMed Central  Google Scholar 

  9. De Boysson H, Boutemy J, Creveuil C et al (2013) Is there a place for cyclophosphamide in the treatment of giant-cell arteritis? A case series and systematic review. Semin Arthritis Rheum 43:105–112

    Article  PubMed  Google Scholar 

  10. De Silva M, Hazleman BL (1986) Azathioprine in giant cell arteritis/polymyalgia rheumatica: a double-blind study. Ann Rheum Dis 45:136–138

    Article  PubMed  PubMed Central  Google Scholar 

  11. Dejaco C, Singh YP, Perel P et al (2015) 2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis 74:1799–1807

    Article  CAS  PubMed  Google Scholar 

  12. Diamantopoulos AP, Haugeberg G, Lindland A et al (2016) The fast-track ultrasound clinic for early diagnosis of giant cell arteritis significantly reduces permanent visual impairment: towards a more effective strategy to improve clinical outcome in giant cell arteritis? Rheumatology (Oxford) 55:66–70

    Article  Google Scholar 

  13. Fritzlen J, Younge B, Weyand CM et al (2015) Second temporal artery biopsies in patients with temporal arteritis (abstract). Arthritis Rheumatol 67(suppl 10). http://acrabstracts.org/abstracts/second-temporal-artery-biopsies-in-patients-with-temporal-arteriitis-ta/. Zugegriffen: 2.9.2016

  14. Gonzalez-Gay MA, Vazquez-Rodriguez TR, Lopez-Diaz MJ et al (2009) Epidemiology of giant cell arteritis and polymyalgia rheumatica. Arthritis Rheum 61:1454–1461

    Article  PubMed  Google Scholar 

  15. Henes JC, Mueller M, Pfannenberg C et al (2011) Cyclophosphamide for large vessel vasculitis: assessment of response by PET/CT. Clin Exp Rheumatol 29:S43–S48

    PubMed  Google Scholar 

  16. Hoffman GS, Cid MC, Rendt-Zagar KE et al (2007) Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis: a randomized trial. Ann Intern Med 146:621–630

    Article  PubMed  Google Scholar 

  17. Hunder GG, Bloch DA, Michel BA et al (1990) The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 33:1122–1128

    Article  CAS  PubMed  Google Scholar 

  18. Jennette JC, Falk RJ, Bacon PA et al (2013) 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 65:1–11

    Article  CAS  PubMed  Google Scholar 

  19. Kermani TA, Schmidt J, Crowson CS et al (2012) Utility of erythrocyte sedimentation rate and C‑reactive protein for the diagnosis of giant cell arteritis. Semin Arthritis Rheum 41:866–871

    Article  CAS  PubMed  Google Scholar 

  20. Kermani TA, Warrington KJ, Crowson CS et al (2013) Large-vessel involvement in giant cell arteritis: a population-based cohort study of the incidence-trends and prognosis. Ann Rheum Dis 72:1989–1994

    Article  PubMed  Google Scholar 

  21. Kermani TA, Warrington KJ, Cuthbertson D et al (2015) Disease relapses among patients with giant cell arteritis: a prospective, longitudinal cohort study. J Rheumatol 42:1213–1217

    Article  PubMed  PubMed Central  Google Scholar 

  22. Klink T, Geiger J, Both M et al (2014) Giant cell arteritis: diagnostic accuracy of MR imaging of superficial cranial arteries in initial diagnosis-results from a multicenter trial. Radiology 273:844–852

    Article  PubMed  Google Scholar 

  23. Koster MJ, Matteson EL, Warrington KJ (2016) Recent advances in the clinical management of giant cell arteritis and Takayasu arteritis. Curr Opin Rheumatol 28:211–217

    Article  PubMed  Google Scholar 

  24. Labarca C, Koster MJ, Crowson CS et al (2016) Predictors of relapse and treatment outcomes in biopsy-proven giant cell arteritis: a retrospective cohort study. Rheumatology (Oxford) 55:347–356

    Article  Google Scholar 

  25. Lally L, Forbess L, Hatzis C et al (2016) A prospective open label phase IIa trial of Tocilizumab in the treatment of polymyalgia rheumatica. Arthritis Rheumatol. doi:10.1002/art.39740

    PubMed  Google Scholar 

  26. Langford C, Cuthbertson D, Ytterberg SR et al (2015) A randomized double-blind trial of abatacept and glucocorticoids for the treatment of giant cell arteritis (abstract). Arthritis Rheumatol 67(suppl 10). http://acrabstracts.org/abstract/a-randomized-double-blind-trial-of-abatacept-and-glucocorticoids-for-the-treatment-of-giant-cell-ateritis/. Zugegriffen: 2.9.2016

  27. Loock J, Henes J, Kotter I et al (2012) Treatment of refractory giant cell arteritis with cyclophosphamide: a retrospective analysis of 35 patients from three centres. Clin Exp Rheumatol 30:S70–S76

    PubMed  Google Scholar 

  28. Loricera J, Blanco R, Hernandez JL et al (2015) Tocilizumab in giant cell arteritis: multicenter open-label study of 22 patients. Semin Arthritis Rheum 44:717–723

    Article  CAS  PubMed  Google Scholar 

  29. Luqmani R, Lee E, Gillet M et al (2015) The role of ultrasound compared to biopsy of temproal arteries in the diagnosis and treatment of gianc cell arteritis: a diagnostic accuracy and cost-effectiveness study (abstract). Arthritis Rheumatol 67(suppl 10). http://acrabstracts.org/abstract/the-role-of-ultrasound-compared-to-biopsy-of-the-temporal-arteries-in-the-diagnosis-and-treatment-of-giant-cell-arteritis-a-diagnocstic-accuracy-and-cost-effectiveness-study/. Zugegriffen: 2.9.2016

  30. Mackie SL, Koduri G, Hill CL et al (2015) Accuracy of musculoskeletal imaging for the diagnosis of polymyalgia rheumatica: systematic review. RMD Open 1:e000100

    Article  PubMed  PubMed Central  Google Scholar 

  31. Mahr AD, Jover JA, Spiera RF et al (2007) Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum 56:2789–2797

    Article  CAS  PubMed  Google Scholar 

  32. Martinez-Taboada VM, Rodriguez-Valverde V, Carreno L et al (2008) A double-blind placebo controlled trial of etanercept in patients with giant cell arteritis and corticosteroid side effects. Ann Rheum Dis 67:625–630

    Article  CAS  PubMed  Google Scholar 

  33. Mekinian A, Comarmond C, Resche-Rigon M et al (2015) Efficacy of biological-targeted treatments in Takayasu arteritis: multicenter, retrospective study of 49 patients. Circulation 132:1693–1700

    Article  CAS  PubMed  Google Scholar 

  34. Meller J, Strutz F, Siefker U et al (2003) Early diagnosis and follow-up of aortitis with [(18)F]FDG PET and MRI. Eur J Nucl Med Mol Imaging 30:730–736

    Article  CAS  PubMed  Google Scholar 

  35. Mori S, Koga Y (2016) Glucocorticoid-resistant polymyalgia rheumatica: pretreatment characteristics and tocilizumab therapy. Clin Rheumatol 35:1367–1375

    Article  PubMed  Google Scholar 

  36. Mukhtyar C, Guillevin L, Cid MC et al (2009) EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis 68:318–323

    Article  CAS  PubMed  Google Scholar 

  37. Ozen G, Inanc N, Unal AU et al (2016) Assessment of the new 2012 EULAR/ACR clinical classification criteria for polymyalgia rheumatica: a prospective multicenter study. J Rheumatol 43:893–900

    Article  PubMed  Google Scholar 

  38. Patil P, Williams M, Maw WW et al (2015) Fast track pathway reduces sight loss in giant cell arteritis: results of a longitudinal observational cohort study. Clin Exp Rheumatol 33:S103–S106

    Google Scholar 

  39. Pipitone N, Versari A, Salvarani C (2008) Role of imaging studies in the diagnosis and follow-up of large-vessel vasculitis: an update. Rheumatology (Oxford) 47:403–408

    Article  CAS  Google Scholar 

  40. Prieto-Gonzalez S, Garcia-Martinez A, Tavera-Bahillo I et al (2015) Effect of glucocorticoid treatment on computed tomography angiography detected large-vessel inflammation in giant-cell arteritis. A prospective, longitudinal study. Medicine (Baltimore) 94:e486

    Article  CAS  PubMed Central  Google Scholar 

  41. Salvarani C, Macchioni P, Manzini C et al (2007) Infliximab plus prednisone or placebo plus prednisone for the initial treatment of polymyalgia rheumatica: a randomized trial. Ann Intern Med 146:631–639

    Article  PubMed  Google Scholar 

  42. Scheel AK, Meller J, Vosshenrich R et al (2004) Diagnosis and follow up of aortitis in the elderly. Ann Rheum Dis 63:1507–1510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Schmidt WA, Natusch A, Moller DE et al (2002) Involvement of peripheral arteries in giant cell arteritis: a color Doppler sonography study. Clin Exp Rheumatol 20:309–318

    CAS  PubMed  Google Scholar 

  44. Schmidt WA, Nerenheim A, Seipelt E et al (2002) Diagnosis of early Takayasu arteritis with sonography. Rheumatology (Oxford) 41:496–502

    Article  CAS  Google Scholar 

  45. Seror R, Baron G, Hachulla E et al (2014) Adalimumab for steroid sparing in patients with giant-cell arteritis: results of a multicentre randomised controlled trial. Ann Rheum Dis 73:2074–2081

    Article  CAS  PubMed  Google Scholar 

  46. Spira D, Xenitidis T, Henes J et al (2016) MRI parametric monitoring of biological therapies in primary large vessel vasculitides: a pilot study. Br J Radiol 89:20150892

    Article  PubMed  Google Scholar 

  47. Terao C, Yoshifuji H, Nakajima T et al (2015) Ustekinumab as a therapeutic option for Takayasu arteritis: from genetic findings to clinical application. Scand J Rheumatol 45(1):80–82. doi:10.3109/03009742.2015.1060521

    Article  Google Scholar 

  48. Unizony SH, Dasgupta B, Fisheleva E et al (2013) Design of the tocilizumab in giant cell arteritis trial. Int J Rheumatol 2013:912562. doi:10.1155/2013/912562

    Article  PubMed  PubMed Central  Google Scholar 

  49. Villiger PM, Adler S, Kuchen S et al (2016) Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 387:1921–1927

    Article  CAS  PubMed  Google Scholar 

  50. Weyand CM, Goronzy JJ (2013) Immune mechanisms in medium and large-vessel vasculitis. Nat Rev Rheumatol 9:731–740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Weyand CM, Goronzy JJ (2014) Giant-cell arteritis and polymyalgia rheumatica. N Engl J Med 371:1653

    Article  PubMed  Google Scholar 

  52. Weyand CM, Hicok KC, Hunder GG et al (1994) Tissue cytokine patterns in patients with polymyalgia rheumatica and giant cell arteritis. Ann Intern Med 121:484–491

    Article  CAS  PubMed  Google Scholar 

  53. Xenitidis T, Horger M, Zeh G et al (2013) Sustained inflammation of the aortic wall despite tocilizumab treatment in two cases of Takayasu arteritis. Rheumatology (Oxford) 52:1729–1731

    Article  CAS  Google Scholar 

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  1. Vaskulitiszentrum Süd, Klinik für Innere Medizin, Rheumatologie und Immunologie, Klinik Kirchheim – Akademisches Lehrkrankenhaus der Universität Tübingen, Eugenstr. 3, 73230, Kirchheim unter Teck, Deutschland

    B. Hellmich

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B. Hellmich gibt an, Prüfarzthonorare von Roche und GSK sowie Vortragshonorare von AbbVie, BMS, Novartis und Roche erhalten und eine Beratertätigkeit für Roche und BMS ausgeübt zu haben.

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Hellmich, B. Management der Polymyalgia rheumatica und der Großgefäßvaskulitiden. Internist 57, 1069–1078 (2016). https://doi.org/10.1007/s00108-016-0131-x

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