The use of subcutaneous methotrexate from various manufacturers in real clinical practice: a comparative study

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Abstract

Background: Methotrexate is the main synthetic disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other immunoinflammatory conditions. In the recent years, the subcutaneous form of methotrexate (SC MTX), particularly as ready-to-use syringes, has been increasingly used worldwide. Currently, several generics of SC MTX from different manufacturers are available. In literature we could not find any publications on the comparison of SC MTX generics.

Aim: To evaluate the possibility to effectively use various SC MTXs for the treatment of RA and PsA in real clinical practice.

Materials and methods: Patients older than 18 years old with a diagnosis of RA by ACR 1987 or ACR / EULAR 2010 criteria or diagnosis of PsA by CASPAR criteria with indications for SC MTX were included in this open-label 6-month observational study “Therapy of Rheumatoid Arthritis with Methotrexate in the Subcutaneous Form in Clinical Practice (TRAMPLIN)”. TRAMPLIN included two study periods: 1) a retrospective study of the safety of SC MTX from various manufacturers in clinical practice, according to patients' medical records; 632 patients (67.2% female, 32.8% male) on SC MTX were identified, and the number of adverse reactions recorded in the documentation (spontaneous reports) was determined; 2) a prospective study of the treatment duration and the reasons for the withdrawal of SC MTX from different manufacturers, which included 69 patients with RA and PsA. SC MTXs from three manufacturers were used in this study, namely Metoject (Medac GmbH, Germany); Métortrites (S.C. Rompharm Company S.R.L., Romania); Methotrexat Ebewe (Sandoz Pharmaceuticals D.D., Slovenia).

Results: In the retrospective part of the study very few adverse events (AEs) were registered, which were related to SC MTX in the physician's opinion (41 patients, or 6.5%). Their incidence was higher in methotrexate-naïve patients. In the prospective part of the study at 3 months after the start of SC MTX therapy, 25 patients (36.2%) changed the treatment regimen (switched between the study drugs or to oral methotrexate). The main reasons for switching (20.3%) were “non-medical” events in the outpatients. AEs ranked second as a reason for the drug withdrawal (14.5%), irrespective of the manufacturer. At 6 month of the study, 38% patients were treated with Metoject, 30% with Methotrexat Ebewe, 28% with Métortrites, and 4% of patients  switched to oral methotrexate.

Conclusion: This first Russian study of SC MTX generics from three different manufacturers confirmed a good SC MTX safety profile in a large clinical sample and showed good retention rates for therapy: by the end of the observation, 96% of the patients with available follow-up data remained on SC MTX. All three SC MTXs from different manufacturers were compatible in terms of safety, tolerability, and drug survival.

About the authors

D. E. Karateev

Moscow Regional Research and Clinical Institute (MONIKI)

Author for correspondence.
Email: dekar@inbox.ru
ORCID iD: 0000-0002-2352-4080

Dmitry E. Karateev – MD, PhD, Head of Department of Rheumatology; Professor, Chair of Therapy, Postgraduate Training Faculty

61/2 Shchepkina ul., Moscow, 129110

 

Russian Federation

E. L. Luchikhina

Moscow Regional Research and Clinical Institute (MONIKI)

Email: eleluch@yandex.ru
ORCID iD: 0000-0002-6519-1106

Elena L. Luchikhina – MD, PhD, Leading Research Fellow, Department of Rheumatology; Associate Professor, Chair of Therapy, Postgraduate Training Faculty

61/2 Shchepkina ul., Moscow, 129110

Russian Federation

G. I. Gridneva

V.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences

Email: galinakugno@rambler.ru
ORCID iD: 0000-0002-0928-3911

Galina I. Gridneva – MD, PhD, Research Fellow, Laboratory of the Study of Comorbid Infections and Monitoring of the Safety of Drug Therapy

34A Kashirskoe shosse, Moscow, 115522

Russian Federation

N. V. Demidova

V.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences

Email: natasha-demidova@mail.ru
ORCID iD: 0000-0002-7414-8513

Natalia V. Demidova – MD, PhD, Senior Research Fellow, Early Arthritis Laboratory

34A Kashirskoe shosse, Moscow, 115522

Russian Federation

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