Recommendations for the Use of Parenteral Methotrexate in Rheumatic Diseases

Jesús Tornero Molina¹, Jaime Calvo², Francisco Javier Ballina-García³, María Ángeles Belmonte⁴, Francisco J. Blanco^5,6, Miguel Angel Caracuel-Ruiz⁷, Jordi Carbonell⁸, Hector Corominas⁹, Eugenio Chamizo Carmona¹⁰, C. Hidalgo-Calleja¹¹, Jose Andres Roman Ivorra¹², José Luis Marenco de la Fuente¹³, J.V. Moreno¹⁴, Santiago Muñoz Fernandez¹⁵, Joan Miquel Nolla¹⁶, Trinidad Perez Sandoval¹⁷, Raimon Sanmarti¹⁸, Pilar Trenor¹⁹, Claudia Urrego²⁰, Javier Vidal¹ and José Rosas²¹, ¹Rheumatology Unit, Hospital de Guadalajara, Guadalajara, Spain, ²Rheumatology Unit, Hospital Universitario Araba, Vitoria-Gasteiz, Spain, ³Department of Rheumatology, Hospital Universitario Central de Asturias, Asturias, Spain, ⁴Rheumatology service, Hospital Regional Universitario Carlos Haya, Malaga, Spain, ⁵Osteoarticular and Aging Research Lab, INIBIC Complejo Hospitalario Universitario A Coruña, A Coruña, Spain, ⁶Rheumatology Division, INIBIC-Complejo Hospitalario Universitario A Coruña (CHUAC), La Coruña, Spain, ⁷Rheumatology service, IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Spain, ⁸Rheumatology Unit, Hospital del Mar, Barcelona, Spain, ⁹Rheumatology, Hospital Moises Broggi, Barcelona, Spain, ¹⁰Rheumatology, Hospital de Mérida, Mérida, Spain, ¹¹University of Salamanca Hospital, Salamanca, Spain, ¹²Department of Rheumatology, Hospital Universitario y Politecnico La Fe, Valencia, Spain, ¹³Rheumatology, Hospital de Valme, Seville, Spain, ¹⁴Rheumatologist. Vall D’Hebron Hospital, Barcelona, Spain, ¹⁵Rheumatology, Hospital Infanta Sofía, Madrid, Spain, ¹⁶Rheumatology, Bellvitge University Hospital, Barcelona, Spain, ¹⁷Rheumatology, Hospital de León, LEÓN, Spain, ¹⁸Rheumatology Department, Hospital Clínic de Barcelona, Barcelona, Spain, ¹⁹Rheumatology Unit, Hospital Clínico de Valencia, Valencia, Spain, ²⁰Hospital G. Segovia, Segovia, Spain, ²¹Rheumatology, Hospital Marina Baixa, Villajoyosa (Alicante), Spain

Meeting: ACR/ARHP Annual Meeting 2016

Date of first publication: September 28, 2016

Keywords: methotrexate (MTX) and rheumatoid arthritis (RA)

Session Information

Date: Tuesday, November 15, 2016

Title: Rheumatoid Arthritis – Clinical Aspects - Poster III: Treatment – Monitoring, Outcomes, Adverse Events

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: To develop recommendations for the management of parenteral MTX in rheumatic diseases based on best evidence and experience.

Methods: A group of 21 experts on parenteral MTX use was selected. The coordinator formulated 13 questions about parenteral MTX (indications, efficacy, safety and cost-effectiveness). A systematic review were performed in order to answer the questions. Using this information, inclusion and exclusion criteria were stablishes as well as the search strategies (Medline, Embase and the Cochrane Library were searched). Three different reviewers selected the articles. Evidence tables were produced. At the same time, EULAR and ACR abstracts were evaluates. With this evidence the coordinator proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation was established using the Oxford Center for Evidence Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no).

Results: A total of 13 preliminary recommendations on the use of parenteral MTX were proposed of which 11 were accepted (see table). Two were not voted and were explained in the main text of the document.

Conclusion: This document pretends to help solve usual clinical questions and facilitate decision making when treating rheumatic patients with parenteral MTX. Table. Recommendations and their level of evidence (LE), grade of recommendation (GR) and grade of agreement (GA).

#	RECOMMENDATION	LE; GR; GA
1	Parenteral MTX biodisponibility compared with oral MTX is superior, mainly if the dose is ≥15 mg/w	NE 2b; GR B-C; GA 100%
2	In MTX-naïve patients, parenteral MTX efficacy compared with oral MTX is superior (doses of 15 mg/w)	NE 1b; GR A; GA 94%
3	In patients refractory to oral MTX (15 mg/w) the efficacy of dose escalation is higher with parenteral MTX	NE 2a; GR B; GA 94%
4	Safety profile and tolerability of parenteral MTX is similar to oral MTX	NE 1b; GR B; GA 100%
5	It is recommended to use parenteral MTX in patients with high disease activity, in those with low adherence to oral MTX, polypharmacy, obese patients, in order to avoid dosing errors, and always taking into account patients preferences	NE 4; GR D; GA 100%
6	It is recommended to initiate, increase and decrease parenteral MTX the same way as with oral MTX	NE 5; GR D; GA 81%
7	It is recommended to increase parenteral MTX dose up to 25-30 mg/w	NE 5; GR D; GA 88%
8	According to available pharmacokinetic data, the dose conversion between oral and parenteral dose would be: up to 15 mg/w the same dose, 20 mg of oral MTX would be 15 mg of parenteral MTX and for 25 mg of oral MTX, 20 mg of parenteral MTX	NE 2b; GR B; GA 100%
9	Subcutaneous MTX could be cost-effective in early RA naive to MTX	NE 2a; GR B; GA 94%
10	Parenteral MTX might increase patients adherence to MTX	NE 2b; GR B; GA 94%
11	Self-administration education provides a high adherence to treatment, satisfaction, patients autonomy and improves and adequate administration	NE 2b; GR B; GA 100%

Disclosure: J. Tornero Molina, None; J. Calvo, None; F. J. Ballina-García, None; M. Á. Belmonte, None; F. J. Blanco, None; M. A. Caracuel-Ruiz, None; J. Carbonell, None; H. Corominas, None; E. Chamizo Carmona, None; C. Hidalgo-Calleja, None; J. A. Roman Ivorra, None; J. L. Marenco de la Fuente, None; J. V. Moreno, None; S. Muñoz Fernandez, None; J. M. Nolla, None; T. Perez Sandoval, None; R. Sanmarti, None; P. Trenor, None; C. Urrego, None; J. Vidal, None; J. Rosas, None.

To cite this abstract in AMA style:

Tornero Molina J, Calvo J, Ballina-García FJ, Belmonte MÁ, Blanco FJ, Caracuel-Ruiz MA, Carbonell J, Corominas H, Chamizo Carmona E, Hidalgo-Calleja C, Roman Ivorra JA, Marenco de la Fuente JL, Moreno JV, Muñoz Fernandez S, Nolla JM, Perez Sandoval T, Sanmarti R, Trenor P, Urrego C, Vidal J, Rosas J. Recommendations for the Use of Parenteral Methotrexate in Rheumatic Diseases [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/recommendations-for-the-use-of-parenteral-methotrexate-in-rheumatic-diseases/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/recommendations-for-the-use-of-parenteral-methotrexate-in-rheumatic-diseases/