nach oben

Rheumatology International

Erschienen in:

20.02.2021 | Imaging

Methotrexate does not increase the risk of liver fibrosis in patients with rheumatoid arthritis: assessment by ultrasound elastography (ARFI-MetRA study)

verfasst von: Martin Feuchtenberger, Lisa Kraus, Axel Nigg, Hendrik Schulze-Koops, Arne Schäfer

Erschienen in: Rheumatology International | Ausgabe 6/2021

Einloggen, um Zugang zu erhalten

Abstract

Objectives

Only limited data are available on the risk of liver fibrosis in patients with rheumatoid arthritis on long-term methotrexate treatment. To assess the risk of liver fibrosis in patients with rheumatoid arthritis treated with methotrexate, non-invasive, ultrasound-based elastography [acoustic radiation force impulse (ARFI) imaging] was applied.

Methods

In total, 119 patients were assessed using acoustic radiation force impulse (ARFI) imaging between July 2018 and April 2019. In a cross-sectional, single-centre study design, ARFI scores were compared between patient subgroups with (n = 65) and without (n = 54) methotrexate exposure. The main outcome variable was the mean fibrosis score as measured by the ARFI method. The mean shear wave velocity was calculated from 10 valid ARFI measurements for each patient. Inferential statistical analyses (between group) were performed using ANOVA for independent samples in the case of continuous outcome variables.

Results

Sixty-five patients with and fifty-four patients without MTX exposure were assessed using the ARFI elastography method. Participating patients on MTX medication (1.113 m/s) showed ARFI scores that were comparable to those of participants without MTX exposure (1.062 m/s); P = 0.228. The mean cumulative dose in the group of MTX-exposed patients was 3602 mg.

Conclusion

The mean value of the repeated determination of liver density using ARFI imaging did not differ significantly between the MTX-exposed and MTX-naive patients with RA. No increased rate of liver fibrosis was found among RA patients treated with MTX.

Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, Yamamoto K (2018) Rheumatoid arthritis. Nat Rev Dis Primers 4:18001. https://doi.org/10.1038/nrdp.2018.1CrossRefPubMed

van Vollenhoven R (2019) Treat-to-target in rheumatoid arthritis—are we there yet? Nat Rev Rheumatol 15(3):180–186. https://doi.org/10.1038/s41584-019-0170-5CrossRefPubMed

Burmester GR, Pope JE (2017) Novel treatment strategies in rheumatoid arthritis. Lancet 389(10086):2338–2348. https://doi.org/10.1016/S0140-6736(17)31491-5CrossRefPubMed

Combe B, Landewe R, Daien CI, Hua C, Aletaha D, Alvaro-Gracia JM, Bakkers M, Brodin N, Burmester GR, Codreanu C, Conway R, Dougados M, Emery P, Ferraccioli G, Fonseca J, Raza K, Silva-Fernandez L, Smolen JS, Skingle D, Szekanecz Z, Kvien TK, van der Helm-van MA, van Vollenhoven R (2017) 2016 update of the EULAR recommendations for the management of early arthritis. Ann Rheum Dis 76:948–959. https://doi.org/10.1136/annrheumdis-2016-210602CrossRefPubMed

Fiehn C, Holle J, Iking-Konert C, Leipe J, Weseloh C, Frerix M, Alten R, Behrens F, Baerwald C, Braun J, Burkhardt H, Burmester G, Detert J, Gaubitz M, Gause A, Gromnica-Ihle E, Kellner H, Krause A, Kuipers J, Lorenz HM, Muller-Ladner U, Nothacker M, Nusslein H, Rubbert-Roth A, Schneider M, Schulze-Koops H, Seitz S, Sitter H, Specker C, Tony HP, Wassenberg S, Wollenhaupt J, Kruger K (2018) S2e guideline: treatment of rheumatoid arthritis with disease-modifying drugs. Z Rheumatol 77:35–53. https://doi.org/10.1007/s00393-018-0481-yCrossRefPubMed

Aithal GP (2011) Hepatotoxicity related to antirheumatic drugs. Nat Rev Rheumatol 7:139–150. https://doi.org/10.1038/nrrheum.2010.214CrossRefPubMed

ICH (2016) Guideline for good clinical practice E6 (R2). ICH harmonised tripartite guideline. Version of December 2016. EMA, London, UK

Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis 69:1580–1588. https://doi.org/10.1136/ard.2010.138461CrossRefPubMed

SPSS (2008) SPSS for windows release 17.0. IBM, Armonk, NY

10.

Friedrich-Rust M, Nierhoff J, Lupsor M, Sporea I, Fierbinteanu-Braticevici C, Strobel D, Takahashi H, Yoneda M, Suda T, Zeuzem S, Herrmann E (2012) Performance of acoustic radiation force impulse imaging for the staging of liver fibrosis: a pooled meta-analysis. J Viral Hepat 19:e212–e219. https://doi.org/10.1111/j.1365-2893.2011.01537.xCrossRefPubMed

11.

Paul SB, Das P, Mahanta M, Sreenivas V, Kedia S, Kalra N, Kaur H, Vijayvargiya M, Ghosh S, Gamanagatti SR, Shalimar GSD, Acharya SK (2017) Assessment of liver fibrosis in chronic hepatitis: comparison of shear wave elastography and transient elastography. Abdom Radiol (NY) 42(12):2864–2873. https://doi.org/10.1007/s00261-017-1213-5CrossRef

12.

Patel V, Sanyal AJ (2013) Drug-induced steatohepatitis. Clin Liver Dis 17:533vii–546vii. https://doi.org/10.1016/j.cld.2013.07.012CrossRef

13.

Bath RK, Brar NK, Forouhar FA, Wu GY (2014) A review of methotrexate-associated hepatotoxicity. J Dig Dis 15:517–524. https://doi.org/10.1111/1751-2980.12184CrossRefPubMed

14.

Curtis JR, Beukelman T, Onofrei A, Cassell S, Greenberg JD, Kavanaugh A, Reed G, Strand V, Kremer JM (2010) Elevated liver enzyme tests among patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate and/or leflunomide. Ann Rheum Dis 69:43–47. https://doi.org/10.1136/ard.2008.101378CrossRefPubMed

15.

Dávila-Fajardo CL, Swen JJ, Barrera JC, Guchelaar HJ (2013) Genetic risk factors for drug-induced liver injury in rheumatoid arthritis patients using low-dose methotrexate. Pharmacogenomics 14:63–73. https://doi.org/10.2217/pgs.12.183CrossRefPubMed

16.

Salliot C, van der Heijde D (2009) Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 68:1100–1104. https://doi.org/10.1136/ard.2008.093690CrossRefPubMed

17.

Hilal G, Akasbi N, Boudouaya H, Salma K, Harzy T (2020) Liver fibrosis in rheumatoid arthritis patients treated with methotrexate. Curr Rheumatol Rev. https://doi.org/10.2174/1573397116666200319155247CrossRefPubMed

18.

Erre GL, Cadoni ML, Meloni P, Castagna F, Mangoni AA, Piga M, Passiu G, Carru C, Zinellu A, Vidili G (2019) Methotrexate therapy is not associated with increased liver stiffness and significant liver fibrosis in rheumatoid arthritis patients: a cross-sectional controlled study with real-time two-dimensional shear wave elastography. Eur J Intern Med 69:57–63. https://doi.org/10.1016/j.ejim.2019.08.022CrossRefPubMed

19.

Lertnawapan R, Chonprasertsuk S, Siramolpiwat S (2019) Association between cumulative methotrexate dose, non-invasive scoring system and hepatic fibrosis detected by fibroscan in rheumatoid arthritis patients receiving methotrexate. Int J Rheum Dis 22:214–221. https://doi.org/10.1111/1756-185x.13442CrossRefPubMed

20.

Kremer JM, Lee JK (1986) The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis. Arthritis Rheum 29:822–831. https://doi.org/10.1002/art.1780290702CrossRefPubMed

21.

Langman G, Hall PM, Todd G (2001) Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury. J Gastroenterol Hepatol 16:1395–1401. https://doi.org/10.1046/j.1440-1746.2001.02644.xCrossRefPubMed

22.

Boffa MJ, Chalmers RJ, Haboubi NY, Shomaf M, Mitchell DM (1995) Sequential liver biopsies during long-term methotrexate treatment for psoriasis: a reappraisal. Br J Dermatol 133:774–778. https://doi.org/10.1111/j.1365-2133.1995.tb02754.xCrossRefPubMed

23.

Malatjalian DA, Ross JB, Williams CN, Colwell SJ, Eastwood BJ (1996) Methotrexate hepatotoxicity in psoriatics: report of 104 patients from Nova Scotia, with analysis of risks from obesity, diabetes and alcohol consumption during long term follow-up. Can J Gastroenterol 10:369–375. https://doi.org/10.1155/1996/213596CrossRefPubMed

24.

Themido R, Loureiro M, Pecegueiro M, Brandão M, Campos MC (1992) Methotrexate hepatotoxicity in psoriatic patients submitted to long-term therapy. Acta Derm Venereol 72:361–364PubMed

25.

Maybury CM, Jabbar-Lopez ZK, Wong T, Dhillon AP, Barker JN, Smith CH (2014) Methotrexate and liver fibrosis in people with psoriasis: a systematic review of observational studies. Br J Dermatol 171:17–29. https://doi.org/10.1111/bjd.12941CrossRefPubMed

26.

El-Serag HB, Tran T, Everhart JE (2004) Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology 126:460–468. https://doi.org/10.1053/j.gastro.2003.10.065CrossRefPubMed

27.

Anderwald C, Bernroider E, Krssak M, Stingl H, Brehm A, Bischof MG, Nowotny P, Roden M, Waldhäusl W (2002) Effects of insulin treatment in type 2 diabetic patients on intracellular lipid content in liver and skeletal muscle. Diabetes 51:3025–3032. https://doi.org/10.2337/diabetes.51.10.3025CrossRefPubMed

28.

Tilling L, Townsend S, David J (2006) Methotrexate and hepatic toxicity in rheumatoid arthritis and psoriatic arthritis. Clin Drug Investig 26:55–62. https://doi.org/10.2165/00044011-200626020-00001CrossRefPubMed

29.

Berends MA, Snoek J, de Jong EM, van de Kerkhof PC, van Oijen MG, van Krieken JH, Drenth JP (2006) Liver injury in long-term methotrexate treatment in psoriasis is relatively infrequent. Aliment Pharmacol Ther 24:805–811. https://doi.org/10.1111/j.1365-2036.2006.03047.xCrossRefPubMed

30.

Verstappen SM, Bakker MF, Heurkens AH, van der Veen MJ, Kruize AA, Geurts MA, Bijlsma JW, Jacobs JW (2010) Adverse events and factors associated with toxicity in patients with early rheumatoid arthritis treated with methotrexate tight control therapy: the CAMERA study. Ann Rheum Dis 69:1044–1048. https://doi.org/10.1136/ard.2008.106617CrossRefPubMed

31.

Rouhi A, Hazlewood G, Shaheen AA, Swain MG, Barber CEH (2017) Prevalence and risk factors for liver fibrosis detected by transient elastography or shear wave elastography in inflammatory arthritis: a systematic review. Clin Exp Rheumatol 35:1029–1036PubMed

32.

Mori S, Arima N, Ito M, Fujiyama S, Kamo Y, Ueki Y (2018) Non-alcoholic steatohepatitis-like pattern in liver biopsy of rheumatoid arthritis patients with persistent transaminitis during low-dose methotrexate treatment. PLoS ONE 13:e0203084. https://doi.org/10.1371/journal.pone.0203084CrossRefPubMedPubMedCentral

33.

Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, Gottlieb A, Koo JY, Lebwohl M, Leonardi CL, Lim HW, Van Voorhees AS, Beutner KR, Ryan C, Bhushan R (2011) Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol 65:137–174. https://doi.org/10.1016/j.jaad.2010.11.055CrossRefPubMed

34.

Laharie D, Seneschal J, Schaeverbeke T, Doutre MS, Longy-Boursier M, Pellegrin JL, Chabrun E, Villars S, Zerbib F, de Lédinghen V (2010) Assessment of liver fibrosis with transient elastography and FibroTest in patients treated with methotrexate for chronic inflammatory diseases: a case–control study. J Hepatol 53:1035–1040. https://doi.org/10.1016/j.jhep.2010.04.043CrossRefPubMed

35.

Alarcón GS, Kremer J, Weinblatt M (2004) Monitoring guidelines for methotrexate-treated rheumatoid arthritis patients: comment on the article by Yazici et al. Arthritis Rheum 50:2710–2710. https://doi.org/10.1002/art.20318CrossRefPubMed

36.

Smolen JS, Landewe RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, McInnes IB, Sepriano A, van Vollenhoven RF, de Wit M, Aletaha D, Aringer M, Askling J, Balsa A, Boers M, den Broeder AA, Buch MH, Buttgereit F, Caporali R, Cardiel MH, De Cock D, Codreanu C, Cutolo M, Edwards CJ, van Eijk-Hustings Y, Emery P, Finckh A, Gossec L, Gottenberg JE, Hetland ML, Huizinga TWJ, Koloumas M, Li Z, Mariette X, Muller-Ladner U, Mysler EF, da Silva JAP, Poor G, Pope JE, Rubbert-Roth A, Ruyssen-Witrand A, Saag KG, Strangfeld A, Takeuchi T, Voshaar M, Westhovens R, van der Heijde D (2020) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 79:685–699. https://doi.org/10.1136/annrheumdis-2019-216655CrossRefPubMed

37.

Wilke WS, Biro JA, Segal AM (1987) Methotrexate in the treatment of arthritis and connective tissue diseases. Cleve Clin J Med 54:327–338. https://doi.org/10.3949/ccjm.54.4.327CrossRefPubMed

38.

Visser K, Katchamart W, Loza E, Martinez-Lopez JA, Salliot C, Trudeau J, Bombardier C, Carmona L, van der Heijde D, Bijlsma JW, Boumpas DT, Canhao H, Edwards CJ, Hamuryudan V, Kvien TK, Leeb BF, Martin-Mola EM, Mielants H, Muller-Ladner U, Murphy G, Ostergaard M, Pereira IA, Ramos-Remus C, Valentini G, Zochling J, Dougados M (2009) Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E initiative. Ann Rheum Dis 68:1086–1093. https://doi.org/10.1136/ard.2008.094474CrossRefPubMed

39.

American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines (2002) Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum 46:328–346. https://doi.org/10.1002/art.10148CrossRef

40.

Visser K, van der Heijde DM (2009) Risk and management of liver toxicity during methotrexate treatment in rheumatoid and psoriatic arthritis: a systematic review of the literature. Clin Exp Rheumatol 27:1017–1025PubMed

41.

Rostom A, Goldkind L, Laine L (2005) Nonsteroidal anti-inflammatory drugs and hepatic toxicity: a systematic review of randomized controlled trials in arthritis patients. Clin Gastroenterol Hepatol 3:489–498. https://doi.org/10.1016/s1542-3565(04)00777-3CrossRefPubMed

42.

McKenna F, Borenstein D, Wendt H, Wallemark C, Lefkowith JB, Geis GS (2001) Celecoxib versus diclofenac in the management of osteoarthritis of the knee. Scand J Rheumatol 30:11–18. https://doi.org/10.1080/030097401750065265CrossRefPubMed

Titel: Methotrexate does not increase the risk of liver fibrosis in patients with rheumatoid arthritis: assessment by ultrasound elastography (ARFI-MetRA study)
verfasst von: Martin Feuchtenberger
Lisa Kraus
Axel Nigg
Hendrik Schulze-Koops
Arne Schäfer
Publikationsdatum: 20.02.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Rheumatology International / Ausgabe 6/2021
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-021-04804-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

24.04.2024 | DGIM 2024 | Kongressbericht | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Methotrexate does not increase the risk of liver fibrosis in patients with rheumatoid arthritis: assessment by ultrasound elastography (ARFI-MetRA study)

Abstract

Objectives

Methods

Results

Conclusion

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Metformin rückt in den Hintergrund

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Thrombophiliescreening – Wenn, dann richtig und nur bei therapeutischer Konsequenz

Bei Senioren mit Prostatakarzinom auf Anämie achten!

Update Innere Medizin

Springer Medizin

Abstract

Objectives

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2021

A hand exercise mobile app for people with rheumatoid arthritis in Turkey: design, development and usability study

Willingness to get the COVID-19 vaccine among patients with rheumatic diseases, healthcare workers and general population in Turkey: a web-based survey

Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial

Atypical presentation of immunoglobulin G4-related disease as subglottic stenosis: a case-based review

Vascular endothelial injury assessed with functional techniques in systemic sclerosis patients with pulmonary arterial hypertension versus systemic sclerosis patients without pulmonary arterial hypertension: a systematic review and meta-analysis

Is it possible to not perform salivary gland biopsy in targeted patients according to unstimulated salivary flow results in patients with suspected Sjögren's syndrome?

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Metformin rückt in den Hintergrund

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Thrombophiliescreening – Wenn, dann richtig und nur bei therapeutischer Konsequenz

Bei Senioren mit Prostatakarzinom auf Anämie achten!

Update Innere Medizin