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Frequency of methotrexate intolerance in rheumatoid arthritis patients using methotrexate intolerance severity score (MISS questionnaire)

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Abstract

The objective of the study was to determine the frequency of methotrexate intolerance in rheumatoid arthritis (RA) patients by applying the methotrexate intolerance severity score (MISS) questionnaire and to see the effect of dose and concomitant use of other disease-modifying antirheumatic drugs (DMARDS) on methotrexate (MTX) intolerance. For the descriptive study, non-probability sampling was carried out in the Female Rheumatology Department of Fauji Foundation Hospital (FFH), Rawalpindi, Pakistan. One hundred and fifty diagnosed cases of RA using oral MTX were selected. The MISS questionnaire embodies five elements: abdominal pain, nausea, vomiting, fatigue and behavioural symptoms. The amplitude of each element was ranked from 0 to 3 being no complaint (0 points), mild (1 point), moderate (2 points) and severe (3 points). A cut-off score of 6 and above ascertained intolerance by the physicians. A total of 33.3 % of the subjects exhibited MTX intolerance according to the MISS questionnaire. Out of which, the most recurring symptom of all was behavioural with a value of 44 % whereas vomiting was least noticeable with a figure of 11 %. About 6.6 % of the women with intolerance were consuming DMARDs in conjunction with MTX. Those using the highest weekly dose of MTX (20 mg) had supreme intolerance with prevalence in 46.2 % of the patients. The frequency of intolerance decreased with a decrease in weekly dose to a minimum of 20 % with 7.5 mg of MTX. MTX intolerance has moderate prevalence in RA patients and if left undetected, the compliance to use of MTX as a first-line therapy will decrease. Methotrexate intolerance is directly proportional to the dose of MTX taken. Also, there is no upstroke seen in intolerance with the use of other disease-modifying agents.

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Change history

  • 27 January 2021

    The Present address of Nibah Fatimah presented in the original version of this article was deleted.

References

  1. Walker BR, Colledge NR, Ralston SH, Penman I (2014) Davidson’s principles and practice of medicine. Elsevier—Health Sciences Division

  2. Ajeganova S, Andersson ML, Frostegard J, Hafstrom I (2013) Disease factors in early rheumatoid arthritis are associated with differential risks for cardiovascular events and mortality depending on age at onset: a 10-year observational cohort study. J Rheumatol 40(12):1958–1966. doi:10.3899/jrheum.130365

    Article  CAS  PubMed  Google Scholar 

  3. Scott DL, Wolfe F, Huizinga TW (2010) Rheumatoid arthritis. Lancet 376(9746):1094–1108. doi:10.1016/S0140-6736(10)60826-4

    Article  PubMed  Google Scholar 

  4. Yamanaka H, Sugiyama N, Inoue E, Taniguchi A, Momohara S (2014) Estimates of the prevalence of and current treatment practices for rheumatoid arthritis in Japan using reimbursement data from health insurance societies and the IORRA cohort (I). Mod Rheumatol 24(1):33–40. doi:10.3109/14397595.2013.854059

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  6. Silman AJ, Pearson JE (2002) Epidemiology and genetics of rheumatoid arthritis. Arthritis Res 4(Suppl 3):S265–S272

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gramling A, O'Dell JR (2012) Initial management of rheumatoid arthritis. Rheum Dis Clin N Am 38(2):311–325. doi:10.1016/j.rdc.2012.05.003

    Article  Google Scholar 

  8. Majithia V, Geraci SA (2007) Rheumatoid arthritis: diagnosis and management. Am J Med 120(11):936–939. doi:10.1016/j.amjmed.2007.04.005

    Article  PubMed  Google Scholar 

  9. Ruderman EM, Nola KM, Ferrell S, Sapir T, Cameron DR (2012) Incorporating the treat-to-target concept in rheumatoid arthritis. J Manag Care Pharm 18(9):1–18

    PubMed  Google Scholar 

  10. Smolen JS, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas D, Burmester G, Combe B, Cutolo M, de Wit M, Dougados M, Emery P, Gibofsky A, Gomez-Reino JJ, Haraoui B, Kalden J, Keystone EC, Kvien TK, McInnes I, Martin-Mola E, Montecucco C, Schoels M, van der Heijde D (2010) Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 69(4):631–637. doi:10.1136/ard.2009.123919

    Article  PubMed  Google Scholar 

  11. Axelsen MB, Eshed I, Horslev-Petersen K, Stengaard-Pedersen K, Hetland ML, Moller J, Junker P, Podenphant J, Schlemmer A, Ellingsen T, Ahlquist P, Lindegaard H, Linauskas A, Dam MY, Hansen I, Horn HC, Ammitzboll CG, Jorgensen A, Krintel SB, Raun J, Krogh NS, Johansen JS, Ostergaard M, group Os (2014) A treat-to-target strategy with methotrexate and intra-articular triamcinolone with or without adalimumab effectively reduces MRI synovitis, osteitis and tenosynovitis and halts structural damage progression in early rheumatoid arthritis: results from the OPERA randomised controlled trial. Ann Rheum Dis. doi:10.1136/annrheumdis-2013-204537

    Article  PubMed  Google Scholar 

  12. Wasserman AM (2011) Diagnosis and management of rheumatoid arthritis. Am Fam Physician 84(11):1245–1252

    PubMed  Google Scholar 

  13. Fiehn C (2009) Methotrexate in rheumatology. Z Rheumatol 68(9):747–756. doi:10.1007/s00393-009-0535-2, quiz 757

    Article  CAS  PubMed  Google Scholar 

  14. Weekly oral methotrexate therapy: raise awareness of fatal dosing errors (2013). Prescrire international 22 (138):126

  15. Chan ES, Cronstein BN (2013) Mechanisms of action of methotrexate. Bull Hosp Jt Dis 71(Suppl 1):S5–S8

    Google Scholar 

  16. MacGregor AJ (1995) Classification criteria for rheumatoid arthritis. Baillieres Clin Rheumatol 9(2):287–304

    Article  CAS  PubMed  Google Scholar 

  17. Bagatini F, Blatt CR, Maliska G, Trespash GV, Pereira IA, Zimmermann AF, Storb BH, Farias MR (2011) Potential drug interactions in patients with rheumatoid arthritis. Rev Bras Reumatol 51(1):20–39

    Article  PubMed  Google Scholar 

  18. Braun J (2011) Methotrexate: optimizing the efficacy in rheumatoid arthritis. Therapeutic advances in musculoskeletal disease 3(3):151–158. doi:10.1177/1759720X11408635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bulatovic M, Heijstek MW, Verkaaik M, van Dijkhuizen EH, Armbrust W, Hoppenreijs EP, Kamphuis S, Kuis W, Egberts TC, Sinnema G, Rademaker CM, Wulffraat NM (2011) High prevalence of methotrexate intolerance in juvenile idiopathic arthritis: development and validation of a methotrexate intolerance severity score. Arthritis Rheum 63(7):2007–2013. doi:10.1002/art.30367

    Article  CAS  PubMed  Google Scholar 

  20. Vezmar S, Becker A, Bode U, Jaehde U (2003) Biochemical and clinical aspects of methotrexate neurotoxicity. Chemotherapy 49(1–2):92–104

    Article  CAS  PubMed  Google Scholar 

  21. Smolen JS, Aletaha D (2010) The assessment of disease activity in rheumatoid arthritis. Clin Exp Rheumatol 28(3 Suppl 59):S18–S27

    PubMed  Google Scholar 

  22. Calasan MB, van den Bosch OF, Creemers MC, Custers M, Heurkens AH, van Woerkom JM, Wulffraat NM (2013) Prevalence of methotrexate intolerance in rheumatoid arthritis and psoriatic arthritis. Arthritis Res Ther 15(6):R217. doi:10.1186/ar4413

    Article  CAS  PubMed  Google Scholar 

  23. Babur Salim SA, Bhatti Raza A (2013) Frequency of methotrexate intolerance in juvenile idiopathic arthritis patients (JIA): an experience using methotrexate intolerance severity score (MISS). US Armed Forces Med J

  24. Agarwal S, Zaman T, Handa R (2009) Retention rates of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis. Singap Med J 50(7):686–692

    CAS  Google Scholar 

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Acknowledgments

We acknowledge Dr. Bulatović and his team (University Medical Centre Utrecht, Utrecht, The Netherlands) who formulated and validated the MISS Questionnaire. We also thank Dr. Usman Feroze Khatana for supporting us, providing his expertise, rendering his kind services at every step of the way and believing in us and our aims.

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Authors and Affiliations

  1. Fauji Foundation Hospital, Jhelum road, Rawalpindi, 46000, Pakistan

    Nibah Fatimah, Babur Salim, Amjad Nasim, Kamran Hussain, Harris Gul & Sarah Niazi

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  1. Nibah Fatimah
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  2. Babur Salim
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  3. Amjad Nasim
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  4. Kamran Hussain
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  5. Harris Gul
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  6. Sarah Niazi
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Correspondence to Nibah Fatimah.

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Fatimah, N., Salim, B., Nasim, A. et al. Frequency of methotrexate intolerance in rheumatoid arthritis patients using methotrexate intolerance severity score (MISS questionnaire). Clin Rheumatol 35, 1341–1345 (2016). https://doi.org/10.1007/s10067-016-3243-8

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  • DOI: https://doi.org/10.1007/s10067-016-3243-8

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