Top

Published in:

Open Access 14-03-2024 | Methotrexate | Patient Opinion

Associations of gender with sexual functioning, loneliness, depression, fatigue and physical function amongst patients suffering from rheumatoid arthritis with a particular focus on methotrexate usage

Authors: Laila T. Bay, Dorthe S. Nielsen, Caroline Flurey, Annamaria Giraldi, Sören Möller, Christian Graugaard, Torkell Ellingsen

Published in: Rheumatology International | Issue 5/2024

Abstract

There is a lack of knowledge regarding methotrexate (MTX) usage in patients with rheumatoid arthritis (RA) and its possible links with gender, disease characterization and sexual functioning, loneliness, fatigue and depression. We, therefore, investigated the associations of gender with physical function, fatigue, depression, loneliness and sexual functioning with a particular focus on MTX usage. A cross-sectional study design was used. Inclusion criteria were RA diagnosis, age above 18 years and available data on MTX treatment 1 year after diagnosis. Data consisted of responses from validated questionnaires regarding physical function, fatigue, depression, loneliness and sexual functioning combined with evaluations from medical records. Data were analysed with linear regression models comparing numerical outcome measures between male and female patients and between MTX users and MTX non-users. Amongst 286 patients with RA (69 men and 217 women), 67.8% were MTX users 1 year after diagnosis. Comparing women and men, both overall and within subgroups of MTX usage, we found significantly more adverse outcomes for women than men in physical functioning at diagnosis and in sexual function, depression, fatigue and physical functioning at enrolment in the study. Gender differences were also present when comparing MTX users with MTX non-users divided by gender. There were only significant differences in the HAQ and loneliness scores when comparing MTX users with MTX non-users. Women with RA had more negative outcomes measured by the selected PROMs compared to men with RA, both overall and in subgroups of users and non-users of MTX. These findings call for sharpened attention to the importance of gender in the treatment and care of patients with RA, as well as in future clinical research.

Maynard C, Mikuls TR, Cannon GW, England BR, Conaghan PG, Ostergaard M et al (2020) Sex differences in the achievement of remission and low disease activity in rheumatoid arthritis. Arthritis Care Res (Hoboken) 72(3):326–333. https://doi.org/10.1002/acr.23873CrossRefPubMed

Intriago M, Maldonado G, Cardenas J, Rios C (2019) Clinical characteristics in patients with rheumatoid arthritis: differences between genders. TheScientificWorldJOURNAL 2019:8103812. https://doi.org/10.1155/2019/8103812CrossRefPubMedPubMedCentral

Jawaheer D, Maranian P, Park G, Lahiff M, Amjadi SS, Paulus HE (2010) Disease progression and treatment responses in a prospective DMARD-naive seropositive early rheumatoid arthritis cohort: does gender matter? J Rheumatol 37(12):2475–2485. https://doi.org/10.3899/jrheum.091432CrossRefPubMedPubMedCentral

Katz PP, Criswell LA (1996) Differences in symptom reports between men and women with rheumatoid arthritis. Arthritis Care Res 9(6):441–448. https://doi.org/10.1002/art.1790090605CrossRefPubMed

Morgacheva O, Furst DE (2012) Women are from venus, men are from Mars: do gender differences also apply to rheumatoid arthritis activity and treatment responses? J Clin Rheumatol 18(5):259–260. https://doi.org/10.1097/RHU.0b013e31825833e0CrossRefPubMed

Smolen JS, Breedveld FC, Burmester GR, Bykerk V, Dougados M, Emery P et al (2016) Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis 75(1):3–15. https://doi.org/10.1136/annrheumdis-2015-207524CrossRefPubMed

Wasko MC, Dasgupta A, Hubert H, Fries JF, Ward MM (2013) Propensity-adjusted association of methotrexate with overall survival in rheumatoid arthritis. Arthritis Rheum 65(2):334–342. https://doi.org/10.1002/art.37723CrossRefPubMedPubMedCentral

Lopez-Olivo MA, Kakpovbia-Eshareturi V, Des Bordes JK, Barbo A, Christensen R, Suarez-Almazor ME (2018) Treating early undifferentiated arthritis: a systematic review and meta-analysis of direct and indirect trial evidence. Arthritis Care Res (Hoboken). 70(9):1355–1365. https://doi.org/10.1002/acr.23474CrossRefPubMed

Romão VC, Canhão H, Fonseca JE (2013) Old drugs, old problems: where do we stand in prediction of rheumatoid arthritis responsiveness to methotrexate and other synthetic DMARDs? BMC Med 11:17. https://doi.org/10.1186/1741-7015-11-17CrossRefPubMedPubMedCentral

10.

Gwinnutt JM, Norton S, Hyrich KL, Lunt M, Barton A, Cordingley L et al (2021) Changes in the illness perceptions of patients with rheumatoid arthritis over the first year of methotrexate therapy. Rheumatology (Oxford) 60(5):2355–2365. https://doi.org/10.1093/rheumatology/keaa615CrossRefPubMed

11.

Walker AM, Funch D, Dreyer NA, Tolman KG, Kremer JM, Alarcón GS et al (1993) Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis. Arthritis Rheum 36(3):329–335. https://doi.org/10.1002/art.1780360307CrossRefPubMed

12.

Yates M, MacGregor AJ, Ledingham J, Norton S, Bechman K, Dennison EM et al (2020) Variation and implications of treatment decisions in early rheumatoid arthritis: results from a nationwide cohort study. Rheumatology (Oxford) 59(8):2035–2042. https://doi.org/10.1093/rheumatology/kez550CrossRefPubMed

13.

Saevarsdottir S, Wallin H, Seddighzadeh M, Ernestam S, Geborek P, Petersson IF et al (2011) Predictors of response to methotrexate in early DMARD naive rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trial. Ann Rheum Dis 70(3):469–475. https://doi.org/10.1136/ard.2010.139212CrossRefPubMed

14.

Drouin J, Haraoui B (2010) Predictors of clinical response and radiographic progression in patients with rheumatoid arthritis treated with methotrexate monotherapy. J Rheumatol 37(7):1405–1410. https://doi.org/10.3899/jrheum.090838CrossRefPubMed

15.

Kvien TK, Uhlig T, Ødegård S, Heiberg MS (2006) Epidemiological aspects of rheumatoid arthritis: the sex ratio. Ann N Y Acad Sci 1069:212–222. https://doi.org/10.1196/annals.1351.019CrossRefPubMed

16.

Hider SL, Silman AJ, Thomson W, Lunt M, Bunn D, Symmons DP (2009) Can clinical factors at presentation be used to predict outcome of treatment with methotrexate in patients with early inflammatory polyarthritis? Ann Rheum Dis 68(1):57–62. https://doi.org/10.1136/ard.2008.088237CrossRefPubMed

17.

Forslind K, Hafström I, Ahlmén M, Svensson B (2007) Sex: a major predictor of remission in early rheumatoid arthritis? Ann Rheum Dis 66(1):46–52. https://doi.org/10.1136/ard.2006.056937CrossRefPubMedPubMedCentral

18.

Maillefert J-F, Puéchal X, Falgarone G, Lizard G, Ornetti P, Solau E et al (2010) Prediction of response to disease modifying antirheumatic drugs in rheumatoid arthritis. Joint Bone Spine 77(6):558–563. https://doi.org/10.1016/j.jbspin.2010.02.018CrossRefPubMed

19.

Pezzato S, Bonetto C, Caimmi C, Tomassi S, Montanari I, Gnatta MG et al (2021) Depression is associated with increased disease activity and higher disability in a large Italian cohort of patients with rheumatoid arthritis. Adv Rheumatol (London, England) 61(1):57. https://doi.org/10.1186/s42358-021-00214-3CrossRef

20.

Cabrera-Marroquin R, Contreras-Yanez I, Alcocer-Castillejos N, Pascual-Ramos V (2014) Major depressive episodes are associated with poor concordance with therapy in rheumatoid arthritis patients: the impact on disease outcomes. Clin Exp Rheumatol 32(6):904–913PubMed

21.

Bay LT, Ellingsen T, Giraldi A, Graugaard C, Nielsen DS (2020) To be lonely in your own loneliness: The interplay between self-perceived loneliness and rheumatoid arthritis in everyday life: A qualitative study. Musculoskeletal Care 18(4):450–458. https://doi.org/10.1002/msc.1480CrossRefPubMed

22.

Evers AWM, Kraaimaat FW, Geenen R, Jacobs JWG, Bijlsma JWJ (2003) Pain coping and social support as predictors of long-term functional disability and pain in early rheumatoid arthritis. Behav Res Ther 41(11):1295–1310. https://doi.org/10.1016/S0005-7967(03)00036-6CrossRefPubMed

23.

Hacihasanoglu Asilar R, Yildirim A, Saglam R, Demirturk Selcuk E, Erduran Y, Sarihan O (2020) The effect of loneliness and perceived social support on medication adherence self-efficacy in hypertensive patients: An example of Turkey. J Vascular Nurs 38(4):183–190. https://doi.org/10.1016/j.jvn.2020.07.003CrossRef

24.

Bay LT, Graugaard C, Nielsen DS, Moller S, Ellingsen T, Giraldi A (2020) Sexual health and dysfunction in patients with rheumatoid arthritis: a cross-sectional single-center study. Sex Med 8(4):615–630. https://doi.org/10.1016/j.esxm.2020.07.004CrossRefPubMedPubMedCentral

25.

von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP et al (2007) Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ 335(7624):806–808. https://doi.org/10.1136/bmj.39335.541782.ADCrossRef

26.

Bendtsen P, Hornquist JO (1994) Rheumatoid arthritis, coping and well-being. Cross-sectional sub-group comparisons and correlational analyses. Scand J Soc Med 22(2):97–106CrossRefPubMed

27.

Sautner J, Puchner R, Alkin A, Pieringer H (2020) Depression: a common comorbidity in women with rheumatoid arthritis-results from an Austrian cross-sectional study. BMJ Open 10(1):e033958. https://doi.org/10.1136/bmjopen-2019-033958CrossRefPubMedPubMedCentral

28.

Nicklin J, Cramp F, Kirwan J, Greenwood R, Urban M, Hewlett S (2010) Measuring fatigue in rheumatoid arthritis: a cross-sectional study to evaluate the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional questionnaire, visual analog scales, and numerical rating scales. Arthritis Care Res (Hoboken) 62(11):1559–1568. https://doi.org/10.1002/acr.20282CrossRefPubMed

29.

Ministry of Higher Education and Science. Danish Code of Conduct for Research Integrity. In: Science MoHEa, editor.2014

30.

Justice tDMo. Act on supplementary provisions to the regulation on the protection of natural persons with regard to the processing of personal data and on the free movement of such data (the Data Protection Act). In: Justice Mo, editor. Copenhagen2018.https://www.datatilsynet.dk/media/7753/danish-data-protection-act.pdf

31.

Keller A, McGarvey EL, Clayton AH (2006) Reliability and construct validity of the changes in sexual functioning questionnaire short-form (CSFQ-14). J Sex Marital Ther 32(1):43–52. https://doi.org/10.1080/00926230500232909CrossRefPubMed

32.

Petersen M, Kristensen E, Giraldi L, Giraldi A (2020) Sexual dysfunction and mental health in patients with multiple sclerosis and epilepsy. BMC Neurol 20(1):41. https://doi.org/10.1186/s12883-020-1625-7CrossRefPubMedPubMedCentral

33.

Russell D, Peplau LA, Cutrona CE (1980) The revised UCLA Loneliness Scale: concurrent and discriminant validity evidence. J Pers Soc Psychol 39(3):472–480. https://doi.org/10.1037//0022-3514.39.3.472CrossRefPubMed

34.

Perry GR (1990) Loneliness and coping among tertiary-level adult cancer patients in the home. Cancer Nurs 13(5):293–302CrossRefPubMed

35.

Lasgaard M (2007) Reliability and validity of the Danish version of the UCLA Loneliness Scale. Personality Individ Differ 42(7):1359–1366. https://doi.org/10.1016/j.paid.2006.10.013CrossRef

36.

Beck AT, Steer RA (1984) Internal consistencies of the original and revised Beck Depression Inventory. J Clin Psychol 40(6):1365–1367CrossRefPubMed

37.

Beck AT, Steer RA, Ball R, Ranieri W (1996) Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Pers Assess 67(3):588–597. https://doi.org/10.1207/s15327752jpa6703_13CrossRefPubMed

38.

Dures EK, Hewlett SE, Cramp FA, Greenwood R, Nicklin JK, Urban M et al (2013) Reliability and sensitivity to change of the Bristol Rheumatoid Arthritis Fatigue scales. Rheumatology (Oxford) 52(10):1832–1839. https://doi.org/10.1093/rheumatology/ket218CrossRefPubMed

39.

Primdahl J, Esbensen BA, Bech B, Pedersen AK, Thurah AD (2019) SAT0718-HPR validation of the danish version of the bristol rheumatoid arthritis fatigue questionnaires. Ann Rheum Dis 78:1460. https://doi.org/10.1136/annrheumdis-2019-eular.3497CrossRef

40.

Bruce B, Fries JF (2005) The health assessment questionnaire (HAQ). Clin Exp Rheumatol 23(5 Suppl 39):S14–S18PubMed

41.

Bruce B, Fries JF (2003) The Stanford Health Assessment Questionnaire: a review of its history, issues, progress, and documentation. J Rheumatol 30(1):167–178PubMed

42.

Thorsen H, Hansen TM, McKenna SP, Sorensen SF, Whalley D (2001) Adaptation into danish of the stanford health assessment questionnaire (HAQ) and the Rheumatoid Arthritis Quality of Life Scale (RAQoL). Scandinavian J Rheumatol 30(2):103–109CrossRef

43.

Sokka T, Toloza S, Cutolo M, Kautiainen H, Makinen H, Gogus F et al (2009) Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study. Arthritis Res Ther 11(1):R7. https://doi.org/10.1186/ar2591CrossRefPubMedPubMedCentral

44.

Barsky AJ, Peekna HM, Borus JF (2001) Somatic symptom reporting in women and men. J Gen Intern Med 16(4):266–275. https://doi.org/10.1046/j.1525-1497.2001.00229.xCrossRefPubMedPubMedCentral

45.

Addis ME, Mahalik JR (2003) Men, masculinity, and the contexts of help seeking. Am Psychol 58(1):5–14. https://doi.org/10.1037/0003-066x.58.1.5CrossRefPubMed

46.

Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS et al (2018) Rheumatoid arthritis. Nat Rev Dis Primers 4:18001. https://doi.org/10.1038/nrdp.2018.1CrossRefPubMed

47.

Olsen LR, Mortensen EL, Bech P (2004) Prevalence of major depression and stress indicators in the Danish general population. Acta Psychiatr Scand 109(2):96–103. https://doi.org/10.1046/j.0001-690x.2003.00231.xCrossRefPubMed

48.

Andresen JB, Graugaard C, Andersson M, Bahnsen MK, Frisch M (2022) Sexual inactivity and dysfunction in denmark: a project SEXUS study. Arch Sex Behav 51(8):3669–3688. https://doi.org/10.1007/s10508-022-02348-xCrossRefPubMed

49.

Aurrecoechea E, Llorca Diaz J, Diez Lizuain ML, McGwin G Jr, Calvo-Alen J (2017) Gender-associated comorbidities in rheumatoid arthritis and their impact on outcome: data from GENIRA. Rheumatol Int 37(4):479–485. https://doi.org/10.1007/s00296-016-3628-7CrossRefPubMed

50.

McQuillan J, Andersen JA, Berdahl TA, Willett J (2022) Associations of rheumatoid arthritis and depressive symptoms over time: are there differences by education, race/ethnicity, and gender? Arthritis Care Res (Hoboken) 74(12):2050–2058. https://doi.org/10.1002/acr.24730CrossRefPubMed

51.

Sigurdsson B, Palsson SP, Aevarsson O, Olafsdottir M, Johannsson M (2015) Validity of gotland male depression scale for male depression in a community study: the Sudurnesjamenn study. J Affect Disord 173:81–89. https://doi.org/10.1016/j.jad.2014.10.065CrossRefPubMed

52.

De Cuyper E, De Gucht V, Maes S, Van Camp Y, De Clerck LS (2016) Determinants of methotrexate adherence in rheumatoid arthritis patients. Clin Rheumatol 35(5):1335–1339. https://doi.org/10.1007/s10067-016-3182-4CrossRefPubMed

53.

Roodenrijs NMT, van der Goes MC, Welsing PMJ, Tekstra J, van Laar JM, Lafeber F et al (2020) Is prediction of clinical response to methotrexate in individual rheumatoid arthritis patients possible? A systematic literature review. Joint Bone Spine 87(1):13–23. https://doi.org/10.1016/j.jbspin.2019.04.002CrossRefPubMed

54.

Almalag H, Abouzaid HH, Alnaim L, Albaqami J, Al Shalhoub R, Almaghlouth I et al (2020) Risk factors associated with methotrexate intolerance in rheumatoid arthritis patients. Open Access Rheumatol 12:193–202. https://doi.org/10.2147/OARRR.S263287CrossRefPubMedPubMedCentral

55.

Wang H, Dwyer-Lindgren L, Lofgren KT, Rajaratnam JK, Marcus JR, Levin-Rector A et al (2012) Age-specific and sex-specific mortality in 187 countries, 1970–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380(9859):2071–2094. https://doi.org/10.1016/S0140-6736(12)61719-XCrossRefPubMed

56.

Sergeant JC, Hyrich KL, Anderson J, Kopec-Harding K, Hope HF, Symmons DPM et al (2018) Prediction of primary non-response to methotrexate therapy using demographic, clinical and psychosocial variables: results from the UK Rheumatoid Arthritis Medication Study (RAMS). Arthritis Res Ther 20(1):147. https://doi.org/10.1186/s13075-018-1645-5CrossRefPubMedPubMedCentral

57.

Jawaheer D, Messing S, Reed G, Ranganath VK, Kremer JM, Louie JS et al (2012) Significance of sex in achieving sustained remission in the consortium of rheumatology researchers of North America cohort of rheumatoid arthritis patients. Arthritis Care Res (Hoboken) 64(12):1811–1818. https://doi.org/10.1002/acr.21762CrossRefPubMed

Title: Associations of gender with sexual functioning, loneliness, depression, fatigue and physical function amongst patients suffering from rheumatoid arthritis with a particular focus on methotrexate usage
Authors: Laila T. Bay
Dorthe S. Nielsen
Caroline Flurey
Annamaria Giraldi
Sören Möller
Christian Graugaard
Torkell Ellingsen
Publication date: 14-03-2024
Publisher: Springer Berlin Heidelberg
Keywords: Methotrexate
Methotrexate
Rheumatoid Arthritis
Fatigue
Mood Disorders
Affective Disorder
Published in: Rheumatology International / Issue 5/2024
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-024-05555-y

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2024

Pattern of disease expression in SLE patients with antiphospholipid antibodies: data from Indian Systemic Lupus Erythematosus Inception cohort (INSPIRE)

How to improve gender equality in rheumatology: boards, mentors, and teamwork

Pancytopenia with aplastic anemia in systemic lupus erythematosus: case series and literature review

Fear of movement and competence frustration mediate the relationship between pain catastrophising and physical function in people living with axSpA: an online cross-sectional survey

Breakthrough SARS-CoV-2 infection and disease flares in patients with rheumatoid arthritis: result from COVAD e-survey study

Promoting physical activity in rheumatoid arthritis through a physiotherapist led behaviour change-based intervention (PIPPRA): a feasibility randomised trial

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials