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17.07.2024 | Azathioprin | Leitthema

Head-to-Head-Studien bei Kollagenosen und Vaskulitiden

verfasst von: Prof. Dr. med. Bernhard Hellmich, Dr. med. Johanna Mucke, Prof. Dr. med. Martin Aringer

Erschienen in: Zeitschrift für Rheumatologie

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Zusammenfassung

Head-to-Head(H2H)-Studien ermöglichen den direkten Vergleich mehrerer Therapiealternativen und schaffen so die evidenzbasierte Grundlage für den Stellenwert einer Therapie im Vergleich zu anderen für eine spezifische Indikation. Sie stellen daher eine wesentliche Ergänzung zu placebokontrollierten Studien dar. Insbesondere unter den nicht durch die pharmazeutische Industrie durchgeführten kontrollierten klinischen Prüfungen finden sich doch eine relevante Anzahl von H2H-Studien bei Kollagenosen und Vaskulitiden, v. a. bei systemischem Lupus erythematodes (SLE), systemischer Sklerose (SSc) und ANCA(antineutrophile zytoplasmatische Antikörper)-assoziierten Vaskulitiden (AAV). Diese Arbeit umfasst eine Übersicht der H2H-Studien bei Kollagenosen und Vaskulitiden mit Einordnung ihrer Bedeutung für die aktuellen Therapiealgorithmen. Für den SLE wurden insbesondere H2H-Studien zur Therapie der Lupusnephritis durchgeführt, die den Stellenwert von niedrig dosiertem Cyclophosphamid und Mycophenolat sowie von Azathioprin für die Erhaltungstherapie festigten. Bei den AAV konnte in den letzten Jahren Rituximab als Induktions- und remissionserhaltende Therapie durch H2H-Studien herausgearbeitet werden, was nun auch Eingang in aktuelle Therapieleitlinien gefunden hat. Weitere Vergleichsstudien sind notwendig, um im Sinne einer personalisierten Medizin für jede Patientin und jeden Patienten das wirksamste und sicherste Medikament wählen zu können.

Appel GB, Contreras G, Dooley MA et al (2009) Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 20:1103–1112. https://doi.org/10.1681/asn.2008101028CrossRefPubMedPubMedCentral

Arends S, Grootscholten C, Derksen RH et al (2012) Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis. Ann Rheum Dis 71:966–973. https://doi.org/10.1136/annrheumdis-2011-200384CrossRefPubMed

Aringer M, Fischer-Betz R, Hiepe F (2013) Statement on the use of mycophenolate mofetil for systemic lupus erythematosus. ZRheumatol 72:575–580CrossRefPubMed

Avunduk AM, Avunduk MC, Varnell ED et al (2003) The comparison of efficacies of topical corticosteroids and nonsteroidal anti-inflammatory drops on dry eye patients: a clinical and immunocytochemical study. Am J Ophthalmol 136:593–602. https://doi.org/10.1016/s0002-9394(03)00326-xCrossRefPubMed

Chen W, Liu Q, Chen W et al (2012) Outcomes of maintenance therapy with tacrolimus versus azathioprine for active lupus nephritis: a multicenter randomized clinical trial. Lupus 21:944–952. https://doi.org/10.1177/0961203312442259CrossRefPubMed

Chung SA, Langford CA, Maz M et al (2021) 2021 American college of rheumatology/vasculitis foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol 73:1366–1383. https://doi.org/10.1002/art.41773CrossRefPubMed

Clements PJ, Furst DE, Wong WK et al (1999) High-dose versus low-dose D‑penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial. Arthritis Rheum 42:1194–1203. https://doi.org/10.1002/1529-0131(199906)42:6%3C1194::Aid-anr16%3E3.0.Co;2-7CrossRefPubMed

Cohen P, Pagnoux C, Mahr A et al (2007) Churg-Strauss syndrome with poor-prognosis factors: A prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients. Arthritis Rheum 57:686–693. https://doi.org/10.1002/art.22679CrossRefPubMed

Contreras G, Pardo V, Leclercq B et al (2004) Sequential therapies for proliferative lupus nephritis. NEnglJMed 350:971–980CrossRefPubMed

10.

Cuadrado MJ, Bertolaccini ML, Seed PT et al (2014) Low-dose aspirin vs low-dose aspirin plus low-intensity warfarin in thromboprophylaxis: a prospective, multicentre, randomized, open, controlled trial in patients positive for antiphospholipid antibodies (ALIWAPAS). Rheumatology (Oxford) 53:275–284. https://doi.org/10.1093/rheumatology/ket313CrossRefPubMed

11.

De Groot K, Rasmussen N, Bacon PA et al (2005) Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 52:2461–2469. https://doi.org/10.1002/art.21142CrossRefPubMed

12.

Dooley MA, Jayne D, Ginzler EM et al (2011) Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. Nenglj Med 365:1886–1895CrossRef

13.

Fauci AS, Haynes BF, Katz P, Wolff SM (1983) Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 98:76–85. https://doi.org/10.7326/0003-4819-98-1-76CrossRefPubMed

14.

Faurschou M, Westman K, Rasmussen N et al (2012) Brief Report: long-term outcome of a randomized clinical trial comparing methotrexate to cyclophosphamide for remission induction in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 64:3472–3477. https://doi.org/10.1002/art.34547CrossRefPubMed

15.

Fu Q, Wu C, Dai M et al (2022) Leflunomide versus azathioprine for maintenance therapy of lupus nephritis: a prospective, multicentre, randomised trial and long-term follow-up. Ann Rheum Dis 81:1549–1555. https://doi.org/10.1136/ard-2022-222486CrossRefPubMed

16.

Furuta S, Nakagomi D, Kobayashi Y et al (2021) Effect of reduced-dose vs high-dose glucocorticoids added to rituximab on remission induction in ANCA-associated vasculitis: a randomized clinical trial. JAMA 325:2178–2187. https://doi.org/10.1001/jama.2021.6615CrossRefPubMed

17.

Ginzler EM, Dooley MA, Aranow C et al (2005) Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. NEnglJMed 353:2219–2228CrossRefPubMed

18.

Ginzler EM, Wofsy D, Isenberg D et al (2010) Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial. Arthritis Rheum 62:211–221CrossRefPubMed

19.

Guillevin L, Cohen P, Mahr A et al (2003) Treatment of polyarteritis nodosa and microscopic polyangiitis with poor prognosis factors: a prospective trial comparing glucocorticoids and six or twelve cylophospahmide pulses in sixty-five patients. Arthritis Rheum 49:93–100CrossRefPubMed

20.

Guillevin L, Pagnoux C, Karras A et al (2014) Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med 371:1771–1780. https://doi.org/10.1056/NEJMoa1404231CrossRefPubMed

21.

Hellmich B, Kausch I, Doehn C et al (2004) Urinary bladder cancer in Wegener’s granulomatosis: is it more than cyclophosphamide? Ann Rheum Dis 63:1183–1185CrossRefPubMedPubMedCentral

22.

Hellmich B, Sanchez-Alamo B, Schirmer JH et al (2024) EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis 83:30–47. https://doi.org/10.1136/ard-2022-223764CrossRefPubMed

23.

Hiemstra TF, Walsh M, Mahr A et al (2010) Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA 304:2381–2388. https://doi.org/10.1001/jama.2010.1658CrossRefPubMed

24.

Hoffman GS, Kerr GS, Leavitt RY et al (1992) Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 116:488–498. https://doi.org/10.7326/0003-4819-116-6-488CrossRefPubMed

25.

Houssiau FA, D’cruz D, Sangle S et al (2010) Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial. AnnRheumDis 69:2083–2089CrossRefPubMed

26.

Houssiau FA, Vasconcelos C, D’cruz D et al (2010) The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. AnnRheumDis 69:61–64CrossRefPubMed

27.

Jayne D, Rasmussen N, Andrassy K et al (2003) A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 349:36–44. https://doi.org/10.1056/NEJMoa020286CrossRefPubMed

28.

Jones RB, Tervaert JW, Hauser T et al (2010) Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 363:211–220. https://doi.org/10.1056/NEJMoa0909169CrossRefPubMed

29.

Jones RB, Hiemstra TF, Ballarin J et al (2019) Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial. Ann Rheum Dis 78:399–405. https://doi.org/10.1136/annrheumdis-2018-214245CrossRefPubMed

30.

Maher TM, Tudor VA, Saunders P et al (2023) Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial. Lancet Respir Med 11:45–54. https://doi.org/10.1016/s2213-2600(22)00359-9CrossRefPubMed

31.

Moawad P, Shamma R, Hassanein D et al (2022) Evaluation of the effect of topical tacrolimus 0.03 % versus cyclosporine 0.05 % in the treatment of dry eye secondary to Sjogren syndrome. Eur J Ophthalmol 32:673–679. https://doi.org/10.1177/1120672121992680CrossRefPubMed

32.

Mok CC, Ho LY, Ying SKY et al (2020) Long-term outcome of a randomised controlled trial comparing tacrolimus with mycophenolate mofetil as induction therapy for active lupus nephritis. Ann Rheum Dis 79:1070–1076. https://doi.org/10.1136/annrheumdis-2020-217178CrossRefPubMed

33.

Monti S, Águeda AF, Luqmani RA et al (2019) Systematic literature review informing the 2018 update of the EULAR recommendation for the management of large vessel vasculitis: focus on giant cell arteritis. RMD open 5:e001003. https://doi.org/10.1136/rmdopen-2019-001003CrossRefPubMedPubMedCentral

34.

Ordi-Ros J, Saez-Comet L, Perez-Conesa M et al (2017) Enteric-coated mycophenolate sodium versus azathioprine in patients with active systemic lupus erythematosus: a randomised clinical trial. Ann Rheum Dis 76:1575–1582CrossRefPubMed

35.

Pagnoux C, Mahr A, Hamidou MA et al (2008) Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med 359:2790–2803. https://doi.org/10.1056/NEJMoa0802311CrossRefPubMed

36.

Pagnoux C, Quemeneur T, Ninet J et al (2015) Treatment of systemic necrotizing vasculitides in patients aged sixty-five years or older: results of a multicenter, open-label, randomized controlled trial of corticosteroid and cyclophosphamide-based induction therapy. Arthritis Rheumatol (hoboken Nj) 67:1117–1127. https://doi.org/10.1002/art.39011CrossRef

37.

Qiu W, Liu Z, Ao M et al (2013) Punctal plugs versus artificial tears for treating primary Sjögren’s syndrome with keratoconjunctivitis SICCA: a comparative observation of their effects on visual function. Rheumatol Int 33:2543–2548. https://doi.org/10.1007/s00296-013-2769-1CrossRefPubMed

38.

Rodríguez Calvo-De-Mora M, Domínguez-Ruiz C, Barrero-Sojo F et al (2022) Autologous versus allogeneic versus umbilical cord sera for the treatment of severe dry eye disease: a double-blind randomized clinical trial. Acta Ophthalmol 100:e396–e408. https://doi.org/10.1111/aos.14953CrossRefPubMed

39.

Ruperto N, Pistorio A, Oliveira S et al (2016) Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis: a randomised trial. Lancet 387:671–678. https://doi.org/10.1016/s0140-6736(15)01021-1CrossRefPubMed

40.

Schirmer JH, Moosig F (2017) S1 guidelines on diagnostics and treatment of ANCA-associated vasculitis. Z Rheumatol 76:75–76. https://doi.org/10.1007/s00393-017-0393-2CrossRefPubMed

41.

Schirmer JH, Sanchez-Alamo B, Hellmich B et al (2023) Systematic literature review informing the 2022 update of the EULAR recommendations for the management of ANCA-associated vasculitis (AAV): part 1‑treatment of granulomatosis with polyangiitis and microscopic polyangiitis. RMD open. https://doi.org/10.1136/rmdopen-2023-003082CrossRefPubMedPubMedCentral

42.

Sircar G, Goswami RP, Sircar D et al (2018) Intravenous cyclophosphamide vs rituximab for the treatment of early diffuse scleroderma lung disease: open label, randomized, controlled trial. Rheumatol (oxford) 57:2106–2113. https://doi.org/10.1093/rheumatology/key213CrossRef

43.

Smith RM, Jones RB, Specks U et al (2023) Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial. Ann Rheum Dis 82:937–944. https://doi.org/10.1136/ard-2022-223559CrossRefPubMed

44.

Steinberg AD, Decker JL (1974) A double-blind controlled trial comparing cyclophosphamide, azathioprine and placebo in the treatment of lupus glomerulonephritis. Arthritis Rheum 17:923–937. https://doi.org/10.1002/art.1780170602CrossRefPubMed

45.

Steinberg AD, Steinberg SC (1991) Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum 34:945–950CrossRefPubMed

46.

Stone JH, Merkel PA, Spiera R et al (2010) Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 363:221–232. https://doi.org/10.1056/NEJMoa0909905CrossRefPubMedPubMedCentral

47.

Sullivan KM, Goldmuntz EA, Keyes-Elstein L et al (2018) Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma. NEnglJMed 378:35–47CrossRefPubMedPubMedCentral

48.

Tashkin DP, Roth MD, Clements PJ et al (2016) Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir med 4:708–719CrossRefPubMedPubMedCentral

49.

Van De Vlekkert J, Hoogendijk JE, Haan RJ et al (2010) Oral dexamethasone pulse therapy versus daily prednisolone in sub-acute onset myositis, a randomised clinical trial. Neuromuscul Disord 20:382–389. https://doi.org/10.1016/j.nmd.2010.03.011CrossRefPubMed

50.

Van Laar JM, Farge D, Sont JK et al (2014) Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA 311:2490–2498. https://doi.org/10.1001/jama.2014.6368CrossRefPubMed

51.

Vencovsky J, Jarosova K, Machacek S et al (2000) Cyclosporine A versus methotrexate in the treatment of polymyositis and dermatomyositis. ScandJRheumatol 29:95–102CrossRefPubMed

52.

Walsh M, Merkel PA, Peh CA et al (2020) Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med 382:622–631. https://doi.org/10.1056/NEJMoa1803537CrossRefPubMedPubMedCentral

53.

Wechsler ME, Akuthota P, Jayne D et al (2017) Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med 376:1921–1932. 10.1056/NEJMoa1702079CrossRefPubMedPubMedCentral

54.

Wechsler ME, Nair P, Terrier B et al (2024) Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. https://doi.org/10.1056/NEJMoa2311155CrossRefPubMed

55.

Závada J, Pesicková SS, Rysavá R et al (2014) Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A. Lupus 23:69–74. https://doi.org/10.1177/0961203313511555CrossRefPubMed

56.

Zhang M, Qi C, Zha Y et al (2019) Leflunomide versus cyclophosphamide in the induction treatment of proliferative lupus nephritis in Chinese patients: a randomized trial. Clin Rheumatol 38:859–867. https://doi.org/10.1007/s10067-018-4348-zCrossRefPubMed

57.

Zheng Z, Zhang H, Peng X et al (2022) Effect of tacrolimus vs intravenous cyclophosphamide on complete or partial response in patients with lupus nephritis: a randomized clinical trial. JAMA Netw Open 5:e224492. https://doi.org/10.1001/jamanetworkopen.2022.4492CrossRefPubMedPubMedCentral

Titel: Head-to-Head-Studien bei Kollagenosen und Vaskulitiden
verfasst von: Prof. Dr. med. Bernhard Hellmich
Dr. med. Johanna Mucke
Prof. Dr. med. Martin Aringer
Publikationsdatum: 17.07.2024
Verlag: Springer Medizin
Schlagwörter: Azathioprin
Azathioprin
Lupusnephritis
Systemische Sklerodermie
Mycophenolat-Mofetil
Systemischer Lupus erythematodes
Wegener-Granulomatose
Wegener-Granulomatose
Vaskulitiden
Vaskulitiden
Rituximab
Rituximab
Kollagenosen
ANCA-assoziierte Vaskulitiden
ANCA-assoziierte Vaskulitiden
Rheumatologie
Orthopädische Rheumatologie
Erschienen in: Zeitschrift für Rheumatologie
Print ISSN: 0340-1855
Elektronische ISSN: 1435-1250
DOI: https://doi.org/10.1007/s00393-024-01537-4

Passend zum Thema

Oral verfügbarer Komplementinhibitor mit hohem Glukokortikoid-Einsparpotenzial bei AAV

Avacopan von CSL Vifor ist der erste oral verfügbare Small-Molecule-Komplementinhibitor zur Behandlung von ANCA (antineutrophile zytoplasmatische Antikörper)-assoziierten Vaskulitiden (AAV). Gezielte Inhibition des Rezeptors C5aR1 ermöglicht einen Wirkansatz mit einem hohen Einsparpotenzial für Glukokortikoide.

Springer Medizin

Zusammenfassung

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Oral verfügbarer Komplementinhibitor mit hohem Glukokortikoid-Einsparpotenzial bei AAV