International Survey to Evaluate Current Options for Subcutaneous Injection of Methotrexate (MTX) and a New Button-Free MTX Autoinjector

References

• Bedoui Y, Guillot X, Sélambarom J, et al. Methotrexate an old drug with new tricks. Int J Mol Sci. 2019;20:5023. doi:10.3390/ijms20205023
   PubMed Web of Science ®Google Scholar
• Tanaka Y, Okuda K, Takeuchi Y, et al. Efficacy and tolerability of subcutaneously administered methotrexate including dose escalation in long-term treatment of rheumatoid arthritis in a Japanese population. Mod Rheumatol. 2023;33(4):680–689. doi:10.1093/mr/roac103
   Web of Science ®Google Scholar
• Warren RB, Mrowietz U, von Kiedrowski R, et al. An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, Phase 3 trial. Lancet. 2017;389(10068):528–537. doi:10.1016/S0140-6736(16)32127-4
   PubMed Web of Science ®Google Scholar
• Bujor AM, Janjua S, LaValley MP, Duran J, Braun J, Felson DT. Comparison of oral versus parenteral methotrexate in the treatment of rheumatoid arthritis: a meta-analysis. PLoS One. 2019;14(9):e0221823. doi:10.1371/journal.pone.0221823
   PubMed Web of Science ®Google Scholar
• Pichlmeier U, Heuer K-U. Subcutaneous administration of methotrexate with a prefilled syringe autoinjector pen results in a higher relative bioavailability compared with oral administration of methotrexate. Clin Exp Rheumatol. 2014;32(4):563–571.
   PubMed Web of Science ®Google Scholar
• Li D, Yang Z, Kang P, Xie X. Subcutaneous administration of methotrexate at high doses makes a better performance in the treatment of rheumatoid arthritis compared with oral administration of methotrexate: a systematic review and meta-analysis. Sem Arthritis Rheum. 2016;45(6):656–662. doi:10.1016/j.semarthrit.2015.11.004
   Web of Science ®Google Scholar
• Otón T, Carmona L, Loza E, Rosario MP, Andreu JL. Use of parenteral methotrexate in rheumatic disease: a systematic review. Reumatol Clin. 2022;18:207–226. doi:10.1016/j.reuma.2020.11.006
   Web of Science ®Google Scholar
• Tanaka Y. Subcutaneous injection of methotrexate: advantages in the treatment of rheumatoid arthritis. Mod Rheumatol. 2022;33(4):633–639. doi:10.1093/mr/roac156
   Web of Science ®Google Scholar
• Bello AE, Perkins EL, Jay R, Efthimiou P. Recommendations for optimizing methotrexate treatment for patients with rheumatoid arthritis. Open Access Rheumatol. 2017;9:67–79. doi:10.2147/OARRR.S131668
   PubMed Web of Science ®Google Scholar
• Pasma A, Schenk CV, Timman R, et al. Non-adherence to disease-modifying antirheumatic drugs is associated with higher disease activity in early arthritis patients in the first year of the disease. Arthritis Res Ther. 2015;17:218. doi:10.1186/s13075-015-0801-4
   Web of Science ®Google Scholar
• Hope HF, Bluett J, Barton A, Hyrich KL, Cordingley L, Verstappen SMM. Psychological factors predict adherence to methotrexate in rheumatoid arthritis; findings from a systematic review of rates, predictors and associations with patient-reported and clinical outcomes. RMD Open. 2016;2(1):e000171. doi:10.1136/rmdopen-2015-000171
   PubMedGoogle Scholar
• Maniadakis N, Toth E, Schiff M, et al. A targeted literature review examining biologic therapy compliance and persistence in chronic inflammatory diseases to identify the associated unmet needs, driving factors, and consequences. Adv Ther. 2018;35(9):1333–1355. doi:10.1007/s12325-018-0759-0
   PubMed Web of Science ®Google Scholar
• Kang J-H, Choi S-E, Xu H, Park D-J, Lee J-K, Lee S-S. Non-adherence to methotrexate was associated with high disease activity and poor health-related outcomes during 4-year follow-up of rheumatoid arthritis patients. Clin Exp Rheumatol. 2022;40(9):1744–1753. doi:10.55563/clinexprheumatol/ir6yds
   Web of Science ®Google Scholar
• Curtis JR, Bykerk VP, Aassi M, Schiff M. Adherence and persistence with methotrexate in rheumatoid arthritis: a systematic review. J Rheumatol. 2016;43(11):1997–2009. doi:10.3899/jrheum.151212
   PubMed Web of Science ®Google Scholar
• Müller S, Wilke T, Fuchs A, et al. Non-persistence and non-adherence to MTX therapy in patients with rheumatoid arthritis: a retrospective cohort study based on German RA patients. Patient Prefer Adherence. 2017;11:1253–1264. doi:10.2147/PPA.S134924
   Web of Science ®Google Scholar
• Generali E, Carrara G, Bortoluzzi A, et al. Non-adherence and discontinuation rate for oral and parenteral methotrexate: a retrospective-cohort study in 8,952 patients with psoriatic arthritis. J Trans Autoimmun. 2021;4:100113. doi:10.1016/j.jtauto.2021.100113
   Google Scholar
• Van den Bemt BJF, Gettings L, Domanska B, Bruggraber R, Mountain I, Kristensen LE. A portfolio of biologic self-injection devices in rheumatology: how patient involvement in device design can improve treatment experience. Drug Deliv. 2019;26(1):384–392. doi:10.1080/10717544.2019.1587043
   PubMed Web of Science ®Google Scholar
• Senbel E, Tropé S, Herman-Demars H, et al. Benefits of switch from oral to subcutaneous route on adherence to methotrexate in patients with rheumatoid arthritis in real life setting. Patient Prefer Adherence. 2021;15:751–760. doi:10.2147/PPA.S301010
   Web of Science ®Google Scholar
• Saraux A, Hudry C, Zinovieva E, Herman-Demars H. Self-I Investigators group. Use of autoinjectors for methotrexate subcutaneous self-injections: high satisfaction level and good compliance in SELF-I study, a randomized, open-label, parallel group study. Rheumatol Ther. 2019;6(1):47–60. doi:10.1007/s40744-018-0134-2
   Web of Science ®Google Scholar
• Liu Y, Söderberg J, Chao J. Adherence to and persistence with adalimumab therapy among Swedish patients with Crohn’s disease. Pharmacy. 2022;10(4):87. doi:10.3390/pharmacy10040087
   Web of Science ®Google Scholar
• Roszkiewicz J, Swacha Z, Smolewska E. Prefilled pen versus prefilled syringe: a pilot study evaluating two different methods of methotrexate subcutaneous injection in patients with JIA. Pediatr Rheumatol. 2020;18(1):64. doi:10.1186/s12969-020-00455-4
   Web of Science ®Google Scholar
• Kivitz A, Cohen S, Dowd JE, et al. Clinical assessment of pain, tolerability, and preference of an autoinjection pen versus a prefilled syringe for patient self-administration of the fully human, monoclonal antibody adalimumab: the TOUCH trial. Clin Ther. 2006;28(10):1619–1629. doi:10.1016/j.clinthera.2006.10.006
   PubMed Web of Science ®Google Scholar
• Borrás-Blasco J, Gracia-Pérez A, Rosique-Robles JD, Castéra MDE, Abad FJ. Acceptability of switching adalimumab from a prefilled syringe to an autoinjection pen. Expert Opin Biol Ther. 2010;10(3):301–307. doi:10.1517/14712590903530633
   PubMed Web of Science ®Google Scholar
• Borrás-Blasco J, Gracia-Pérez A, Castéra MDE, Rosique-Robles, D, Abad, J . Educational session as a tool to increase patients satisfaction of switching etanercept from the prefilled syringe to the autoinjection pen. Expert Opin Biol Ther. 2013;13(8):1103–1108. doi:10.1517/14712598.2013.795942
   PubMed Web of Science ®Google Scholar
• Ghil J, Zielinska A, Lee Y. Usability and safety of SB5 (an adalimumab biosimilar) prefilled syringe and autoinjector in patients with rheumatoid arthritis. Curr Med Res Opin. 2019;35(3):497–502. doi:10.1080/03007995.2018.1560211
   PubMed Web of Science ®Google Scholar
• Tornero Molina J, López Robledillo JC, Ruiz NC. Potential benefits of the self-administration of subcutaneous methotrexate with autoinjector devices for patients. A review. Drug Healthc Patient Saf. 2021;13:81–94. doi:10.2147/DHPS.S290771
   PubMed Web of Science ®Google Scholar
• Schiff M, Jaffe J, Freundlich B, Madsen P. New autoinjector technology for the delivery of subcutaneous methotrexate in the treatment of rheumatoid arthritis. Expert Rev Med Devices. 2014;11(5):447–455. doi:10.1586/17434440.2014.929492
   Web of Science ®Google Scholar
• Andre AD, Brand-Schieber E, Ramirez M, Munjal S, Kumar R. Subcutaneous sumatriptan delivery devices: comparative ease of use and preference among migraineurs. Patient Prefer Adherence. 2017;11:121–129. doi:10.2147/PPA.S125137
   PubMed Web of Science ®Google Scholar
• M3 Global Research. Frequently Asked Questions. Available from: https://m3globalresearch.com/faq. Accessed January 12, 2024.
   Google Scholar
• Demary W, Schwenke H, Rockwitz K, et al. Subcutaneously administered methotrexate for rheumatoid arthritis, by prefilled syringes versus prefilled pens: patient preference and comparison of the self-injection experience. Patient Prefer Adherence. 2014;8:1061–1071. doi:10.2147/PPA.S64111
   PubMed Web of Science ®Google Scholar
• Fleischmann RM, Bock AE, Zhang W, et al. Usability study of PF-06410293, an adalimumab biosimilar, by prefilled pen: open-label, single-arm, sub-study of a phase 3 trial in patients with rheumatoid arthritis. Rheumatol Ther. 2022;9(3):839–850. doi:10.1007/s40744-022-00439-8
   Web of Science ®Google Scholar
• Vermeire S, D’heyghere F, Nakad A, et al. Preference for a prefilled syringe or an auto-injection device for delivering golimumab in patients with moderate-to-severe ulcerative colitis: a randomized crossover study. Patient Prefer Adherence. 2018;12:1193–1202. doi:10.2147/PPA.S154181
   PubMed Web of Science ®Google Scholar
• Pachon JA, Kivitz AJ, Heuer K-U, Pichlmeier U. Assessing usability, label comprehension, pen robustness and pharmacokinetics of a self-administered prefilled autoinjector pen of methotrexate in patients with rheumatoid arthritis. SAGE Open Med. 2014;2:2050312114564241. doi:10.1177/2050312114564241
   Google Scholar
• Hudry C, Lebrun A, Moura B, Zinovieva E, Backers O, Herman-Demars H. Evaluation of usability and acceptance of a new autoinjector intended for methotrexate subcutaneous self-administration in the management of rheumatoid arthritis. Rheumatol Ther. 2017;4:183–194. doi:10.1007/s40744-017-0057-3
   PubMed Web of Science ®Google Scholar
• Müller-Ladner U, Flipo RM, Vincendron P, Brault Y, Kielar D. Comparison of patient satisfaction with two different etanercept delivery systems. A randomised controlled study in patients with rheumatoid arthritis. Z Rheumatol. 2012;71(10):890–899. doi:10.1007/s00393-012-1034-4
   PubMed Web of Science ®Google Scholar
• Usach I, Martinez R, Festini T, Peris J-E. Subcutaneous injection of drugs: literature review of factors influencing pain sensation at the injection site. Adv Ther. 2019;36(11):2986–2996. doi:10.1007/s12325-019-01101-6
   PubMed Web of Science ®Google Scholar
• Müller-Ladner U, Rockwitz K, Brandt-Jürgens J, et al. Tolerability and patient/physician satisfaction with subcutaneously administered methotrexate provided in two formulations of different drug concentrations in patients with rheumatoid arthritis. Open Rheumatol J. 2010;4:15–22. doi:10.2174/1874312901004010015
   Google Scholar
• McKeage K, Lyseng-Williamson KA. Methotrexate pre-filled autoinjector pen (Nordimet®) for subcutaneous injection: a profile of its use in the EU. Drugs Ther Perspect. 2018;34:197–202. doi:10.1007/s40267-018-0505-3
   Google Scholar
• Tischer B, Mehl A. Patients’ and nurses’ preferences for autoinjectors for rheumatoid arthritis: results of a European survey. Patient Prefer Adherence. 2018;12:1413–1424. doi:10.2147/PPA.S169339
   PubMed Web of Science ®Google Scholar
• Fenwick S, Thakur K, Munro D. Nurse and patient perceptions and preferences for subcutaneous autoinjectors for inflammatory joint or bowel disease: findings from a European survey. Rheumatol Ther. 2019;6(2):195–206. doi:10.1007/s40744-019-0144-8
   PubMed Web of Science ®Google Scholar
• Egeth M, Soosaar J, Nash P, et al. Patient and healthcare professionals preference for Brenzys vs. Enbrel autoinjector for rheumatoid arthritis: a randomized crossover simulated-use study. Adv Ther. 2017;34(5):1157–1172. doi:10.1007/s12325-017-0523-x
   PubMed Web of Science ®Google Scholar
• Zeitoun J-D, Morvan Y. Patients’ perceptions and preferences regarding two different forms of methotrexate autoinjectors for moderate to severe rheumatoid arthritis: a European crossover survey. Patient Prefer Adherence. 2020;14:2177–2185. doi:10.2147/PPA.S269575
   Web of Science ®Google Scholar
• Domanska B, VanLunen B, Peterson L, Mountian I, Schiff M. Comparative usability study for a certolizumab pegol autoinjection device in patients with rheumatoid arthritis. Expert Opin Drug Deliv. 2017;14(1):15–22. doi:10.1080/17425247.2016.1256283
   PubMed Web of Science ®Google Scholar
• Thakur K, Biberger A, Handrich A, Rezk MF. Patient perceptions and preferences of two etanercept autoinjectors for rheumatoid arthritis: findings from a patient survey in Europe. Rheumatol Ther. 2016;3(2):245–256. doi:10.1007/s40744-016-0048-9
   PubMed Web of Science ®Google Scholar
• Thakur K, Biberger A, Handrich A, Rezk MF. Perceptions and preferences of two etanercept autoinjectors for rheumatoid arthritis: a new European Union-approved etanercept biosimilar (Benepali®) versus etanercept (Enbrel®) – findings from a nurse survey in Europe. Rheumatol Ther. 2016;3(1):77–89. doi:10.1007/s40744-016-0035-1
   PubMed Web of Science ®Google Scholar
• Xiao X, Li W, Clawson C, et al. Evaluation of performance, acceptance, and compliance of an auto-injector in healthy and rheumatoid arthritic subjects measured by a motion capture system. Patient Prefer Adherence. 2018;12:515–526. doi:10.2147/PPA.S160394
   PubMed Web of Science ®Google Scholar
• Karlsdottir K, Gunnarsdottir AI, Grondal G, et al. A patients’ perspective towards the injection devices for Humira® and Imraldi® in a nationwide switching program. Front Med. 2022;9:799494. doi:10.3389/fmed.2022.799494
   PubMed Web of Science ®Google Scholar
• Arshad N, Ahmad NM, Saeed MA, Khan S, Batool S, Farman S. Adherence to methotrexate therapy in rheumatoid arthritis. Pak J Med Sci. 2016;32(2):413–417. doi:10.12669/pjms.322.9566
   Web of Science ®Google Scholar
• Coyne M, Rinaldi A, Brigham K, et al. Impact of routines and rituals on burden of treatment, patient training, cognitive load, and anxiety in self-injected biologic therapy. Patient Prefer Adherence. 2022;16:2593–2607. doi:10.2147/PPA.S375037
   PubMed Web of Science ®Google Scholar
• Schiff M, Saunderson S, Mountian I, Hartley P. Chronic disease and self-injection: ethnographic investigations into the patient experience during treatment. Rheumatol Ther. 2017;4(2):445–463. doi:10.1007/s40744-017-0080-4
   PubMed Web of Science ®Google Scholar
• Feagan BG, Marabani M, Wu JJ, Faccin F, Spronk C, Castaneda-Hernández G. The challenges of switching therapies in an evolving multiple biosimilar landscape: a narrative review of current evidence. Adv Ther. 2020;37(11):4491–4518. doi:10.1007/s12325-020-01472-1
   PubMed Web of Science ®Google Scholar
• Reich K, Sorbe C, Griese L, Reich JLK, Augustin M. The value of subcutaneous vs. oral methotrexate: real-world data from the German psoriasis registry PsoBest. Br J Dermatol. 2021;184(4):765–767. doi:10.1111/bjd.19690
   Web of Science ®Google Scholar
• Patil P, Parker RA, Rawcliffe C, et al. Methotrexate-induced nausea and vomiting in adolescent and young adult patients. Clin Rheumatol. 2014;33(3):403–407. doi:10.1007/s10067-013-2389-x
   PubMed Web of Science ®Google Scholar
• Falvey S, Shipman L, Ilowite N, Beukelman T. Methotrexate-induced nausea in the treatment of juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2017;15(1):52. doi:10.1186/s12969-017-0180-2
   Google Scholar