Analysis of methotrexate use practice in patients with rheumatoid arthritis and psoriatic arthritis

Background. Pharmacoepidemiological studies play a key role in optimizing pharmacotherapy for various diseases. In particular, significant progress in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) necessitates a detailed analysis of the consumption of disease-modifying antirheumatic drugs. The modern therapeutic concept for these conditions focuses on achieving and maintaining long-term remission, which positions methotrexate (MTX) as a first-line agent, characterized by high effectiveness, safety and advantageous pharmacoeconomic profiles.

Objective: to investigate the characteristics of MTX use in real clinical practice among patients with RA and PsA during outpatient medical care.

Material and methods. The study comprised two parts: a retrospective cross-sectional analysis of MTX consumption dynamics in 2018, 2020, and 2023 via ATC/DDD (Anatomical Therapeutic Chemical classification, ATC; defined daily dose, DDD) methodology, and a longitudinal non-interventional pharmacoepidemiological study conducted in 2023 using the medical information system “BARS. Healthcare”.

Results. The ATC/DDD analysis demonstrated a significant increase in MTX consumption among patients with RA and PsA: from 302,428.6 to 319,114.3 DDDs per 1,000 patients per year for RA, and from 28,157.1 to 310,771.6 DDDs per 1,000 patients per year for PsA in 2018 and 2023, respectively. The most frequently prescribed dose of MT was 15 mg/week. The primary therapeutic combination for 55.8% of patients was “MT + nonsteroidal anti-inflammatory drugs”, with 32.7% of patients also receiving glucocorticoids (GCs) as part of this combination. The study identified a high frequency of prescriptions for proton pump inhibitors, GCs, and cholecalciferol, highlighting the activity of diseases under consideration, potential complications, and the necessity for the prevention of clinically significant drug interactions.

Conclusions. The conducted study confirmed that MTX remains the main drug for the treatment of RA and PsA. The ATC/DDD analysis demonstrated a significant increase in MTX consumption in recent years, correlating with its therapeutic effectiveness and accessibility. The high frequency of concomitant prescriptions underscores the complexity of treating RA and PsA and the need for an interdisciplinary approach to ensure safety and efficacy of the therapy.

1. Rachina S.A., Kozlov R.S., Belkova Yu.A. Pharmacoepidemiology: from theory to practice. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2014; 7 (1): 33–9 (in Russ.).

2. Bilgin E., Duran E., Bolek E.C., et al. AB0742 conventional synthetic DMARDs in psoriatic arthritis – changing practice in biologic era: real-life results from HURBIO-PsA registry. Ann Rheum Dis. 2020; 79 (Suppl. 1): 1667.1. http://doi.org/10.1136/annrheumdis-2020-eular.4735.

3. Anghel L.A. Utilization patterns of disease-modifying antirheumatic drugs (DMARDs) in patients with autoimmune rheumatic diseases. Farmacia. 2019; 67 (1): 184–92. http://dx.doi.org/10.31925/farmacia.2019.1.25.

4. Chichasova N.V., Lila A.M. Methotrexate in the treatment of rheumatoid arthritis and psoriatic arthritis. Lechaschi vrach. 2020; 7: 42–51 (in Russ.). https://doi.org/10.26295/OS.2020.12.42.002.

5. Nasonov E.L., Amirjanova V.N., Olyunin Y.A., et al. The use of methotrexate in rheumatoid arthritis. Recommendations of the All-Russian public organization “Association of Rheumatologists of Russia”. Rheumatology Science and Practice. 2023; 61 (4): 435–49 (in Russ.). https://doi.org/10.47360/1995-4484-2023-435-449.

6. Ng B., Chu A., Khan M.M. A retrospective cohort study: 10-year trend of disease-modifying antirheumatic drugs and biological agents use in patients with rheumatoid arthritis at Veteran Affairs Medical Centers. BMJ Open. 2013; 3 (4): e002468. http://doi.org/10.1136/bmjopen-2012-002468.

7. Fassmer A.M., Garbe E., Schmedt N. Frequency and trends of disease-modifying antirheumatic drug (DMARD) use in Germany. Pharmacol Res Perspect. 2016; 4 (5): e00254. http://doi.org/10.1002/prp2.254.

8. Jin X.M., Lee J., Choi N.K., et al. Utilization patterns of disease-modifying antirheumatic drugs in elderly rheumatoid arthritis patients. J Korean Med Sci. 2014; 29 (2): 210–6. https://doi.org/10.3346/jkms.2014.29.2.210.

9. Ziganshina L.E., Magsumova D.R., Kurchaeva A.V., et al. ATC/DDD-classification system in pharmacoepidemiological studies. Kachestvennaya klinicheskaya praktika / Good Clinical Practice. 2004; 1: 28–33 (in Russ.).

10. Elseviers M., Wettermark B., Almarsdóttir A.B., et al. Drug utilization research: methods and applications. Wiley-Blackwell; 2016: 536 pp.

11. ATC/DDD Index. Norwegian Institute of Public Health WHO Collaborating Centre for Drug Statistics Methodology. Available at: https://atcddd.fhi.no/atc_ddd_index/?code=L04AX03&showdescription=yes (accessed 16.07.2024).

12. Guidelines for ATC classification and DDD assignment. Norwegian Institute of Public Health WHO Collaborating Centre for Drug Statistics Methodology. Available at: https://atcddd.fhi.no/atc_ddd_index_and_guidelines/guidelines/ (accessed 16.07.2024).

13. The territorial body of the Federal State Statistics Service for the Kaliningrad Region. Population. Available at: https://39.rosstat.gov.ru/population (in Russ.) (accessed 16.07.2024).

14. Hollingworth S., Kairuz T. Measuring medicine use: applying ATC/DDD methodology to real-world data. Pharmacy. 2021; 9 (1): 60. https://doi.org/10.3390/pharmacy9010060.

15. Almutairi K., Nossent J., Preen D., et al. POS0632 The longitudinal associations of methotrexate and biologic use on hospital admission for rheumatoid arthritis patients in Western Australia population (1995–2014). Ann Rheum Dis. 2021; 80 (Suppl. 1): 554. https://doi.org/10.1136/annrheumdis-2021-eular.3230.

16. Won S., Cho S.K., Kim D., et al. Update on the prevalence and incidence of rheumatoid arthritis in Korea and an analysis of medical care and drug utilization. Rheumatol Int. 2018; 38 (4): 649–56. https://doi.org/10.1007/s00296-017-3925-9.

17. Khraishi M., Ivanovic J., Zhang Y., et al. Real-world utilization of methotrexate or prednisone co-therapy with etanercept among Canadian patients with rheumatoid arthritis: a retrospective cohort study. Curr Med Res Opin. 2019; 35 (11): 2025–33. https://doi.org/10.1080/03007995.2019.1636543.

18. Lee M.P., Lii J., Jin Y., et al. Patterns of systemic treatment for psoriatic arthritis in the US: 2004–2015. Arthritis Care Res. 2018; 70 (5): 791–6. https://doi.org/10.1002/acr.23337.

19. Fraenkel L., Bathon J.M., England B.R., et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2021; 73 (7): 1108–23. https://doi.org/10.1002/art.41752.

20. Tarp S., Jorgensen T.S., Furst D.E., et al. Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients: a systematic review and meta-analysis of randomised trials. Semin Arthritis Rheum. 2019; 48 (6): 958–66. https://doi.org/10.1016/j.semarthrit.2018.10.002.

21. Smolen J.S., Landewé R.B.M., Bijlsma J.W.J., et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020; 79 (6): 685–99. https://doi.org/10.1136/annrheumdis-2019-216655.

22. Gottlieb A., Merola J.F. Psoriatic arthritis for dermatologists. J Dermatolog Treat. 2020; 31 (7): 662–79. http://dx.doi.org/10.1080/09546634.2019.1605142.

23. Coates L.C., Kavanaugh A., Mease P.J., et al. Group for research and assessment of psoriasis and psoriatic arthritis 2015 treatment recommendations for psoriatic arthritis. Arthritis Rheumatol. 2016; 68 (5): 1060–71. https://doi.org/10.1002/art.39573.

24. Montag K., Gingold M., Boers A., Littlejohn G. Disease-modifying anti-rheumatic drug usage, prescribing patterns and disease activity in rheumatoid arthritis patients in community-based practice. Intern Med J. 2011; 41 (6): 450–5. https://doi.org/10.1111/j.1445-5994.2010.02240.x.

25. Karateev A.1, Ermakova Yu.A.1, Berezyuk A.N. Methotrexate and proton pump inhibitors: are there any negative pharmacologial effects? Scientific and Practical Rheumatology. 2013; 51 (6): 662–5 (in Russ.).

26. Iwaki M., Shimada H., Irino Y., et al. Inhibition of methotrexate uptake via organic anion transporters OAT1 and OAT3 by glucuronides of nonsteroidal anti-inflammatory drugs. Biol Pharm Bull. 2017; 40 (6): 926–31. http://doi.org/10.1248/bpb.b16-00970.

27. Tracy T., Krohn K., Jones D., et al. The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis. Eur J Clin Pharmacol. 1992; 42 (2): 121–5. https://doi.org/10.1007/bf00278469.

28. Bagatini F., Blatt C.R., Maliska G., et al. Potential drug interactions in patients with rheumatoid arthritis. Rev Bras Reumatol. 2011; 51 (1): 29–39. http://doi.org/10.1590/S0482-50042011000100003.

29. Instructions for medical use of the drug Methotrexate-RONC®. The State Register of Medicines. Available at: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=0f1ca4f4-7407-4900-85de-e873e382f622 (in Russ.) (accessed 16.07.2024).