Drug Survival and Toxicity of Methotrexate Monotherapy in Daily Clinical Practice. Results from an Early Arthritis Clinic

Christian A. Waimann^1,2, Margarita Landi³, Fernando Dal Pra³, Gustavo Citera⁴, Maria Celeste Orozco⁴, Osvaldo Luis Cerda³, Federico Ceccatto⁵, Sergio Paira⁵, Francisco Colombres⁶, Alberto Berman⁷, Horacio Berman⁷, Anastasia Secco⁸, Marta Mamani⁸, Maritza Manzano⁸, Maria Victoria Martire⁸, Francisco Caeiro⁹, Maria Haye Salinas¹⁰, Alejandro J. Alvarellos¹⁰, Ana C. Alvarez¹⁰, Javier Rosa¹¹, Valeria Scaglioni¹², Enrique R. Soriano¹¹, Josefina Marcos¹³, Mercedes Argentina García¹⁴, AC Costi¹⁵, Alejandro Martinez¹⁶, Oscar Luis Rillo¹⁶, Edson Veloso¹⁷, Ricardo V. Juárez¹⁸, Maria Elena Crespo¹⁹, Ana Quinteros²⁰, Doralia Vasquez²⁰, C Ledesma²¹, Gabriela Salvatierra²¹, R Quintana²², Monica Sacnun²³ and Marcelo Abdala²⁴, ¹Rheumatology, Hospital Dr. Hector Cura, Olavarria, Argentina, ²Rheumatology section, Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, ³Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, ⁴Rheumatology, Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, ⁵Hospital Jose Maria Cullen, Santa Fe, Argentina, ⁶Tucuman, Centro Médico Privado de Reumatología, Tucumán, Argentina, ⁷Centro Médico Privado de Reumatología, Tucumán, Argentina, ⁸Rheumatology, Hospital Bernardino Rivadavia, Buenos Aires, Argentina, ⁹Reumatología, Hospital Privado de Córdoba, Córdoba, Argentina, ¹⁰Rheumatology, Hospital Privado de Córdoba, Córdoba, Argentina, ¹¹Hospital Italiano, Buenos Aires, Argentina, ¹²Rheumatology, Hospital Italiano, Buenos Aires, Argentina, ¹³HIGA San Martín, La Plata, Argentina, ¹⁴Rheumatology Unit, HIGA San Martín, La Plata, Argentina, ¹⁵Rheumatology, HIGA San Martín, La Plata, Argentina, ¹⁶Rheumatology, Hospital General de Agudos “Dr. Ignacio Pirovano”, Buenos Aires, Argentina, ¹⁷Sanatorio y Universidad Adventista Del Plata, Entre Rios, Argentina, ¹⁸Rheumatology Section, Hospital Señor del Milagro, Salta, Argentina, ¹⁹Hospital Señor del Milagro, Salta, Argentina, ²⁰Centro Integral De Reumatologia, Tucumán, Argentina, ²¹Instituto Provincial De Rehabilitación Integral, Santiago del Estero, Argentina, ²²Rheumatology, Hosp. Provincial, Rosario, Argentina, ²³Hosp. Provincial, Rosario, Argentina, ²⁴Hospital Provincial del Centenario, Santa Fe, Argentina

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: drug therapy and methotrexate (MTX), Early Rheumatoid Arthritis

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Clinical Aspects Poster I

Session Type: ACR Poster Session A

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

Background/Purpose: Several trials had reported the efficacy and toxicity of methotrexate monotherapy in patients with early rheumatoid arthritis. However, patients outside clinical trials could be more complex and heterogeneous, with a wide range of comorbidities and clinical characteristics. The aim of our study was to estimate the drug survival and toxicity of methotrexate monotherapy in real life setting.

Methods: We included a cohort of DMARDs naïve patients with diagnosis of early rheumatoid arthritis (RA) of less than 2 years of disease duration. Data was collected every 3 months, including sociodemographic characteristics, functional status, disease activity and medication (dose, treatment strategy and toxicity). The primary outcome was methotrexate monotherapy survival. Time to outcome was assessed from treatment initiation to the end of methotrexate monotherapy (drug suspension or addition of DMARDs/biologics) or last follow-up. Kaplan-Meier product limit method was used to estimate outcome probability. Cox proportional hazards models were fit to determine possible predictors of methotrexate monotherapy survival. A p-value of 0.05 was considered statistically significant.

Results: We included 563 DMARDs (disease-modifying antirheumatic drugs) naive patients with early rheumatoid arthritis. Mean follow-up was 24 ± 16 months. Mean age was 51 ± 14 years, 82% were female and disease duration was 7 ± 6 months. Baseline DAS28 and HAQ were 4.0 ± 1.2 and 0.9 ± 0.6, respectively. Methotrexate (MTX) was the most frequently DMARD used [505 (90%)], followed by Leflunomide [LFN, 193 (34%)], Hydroxychloroquine [HCQ, 105 (19%)] and Sulfazalazine [SFZ, 22 (4%)]. When analyzing treatment strategy, first choice was Methotrexate monotherapy in 384 (68%) of the cases. MTX mean dose was 16 ± 4 mg/week and 44% used MTX doses higher or equal than 20 mg/week. One hundred and fifty patients (40%) had to stop methotrexate monotherapy, with a median survival of 26 months (failure rate = 0.027/patient-months of follow-up). Main reasons for suspension were as follow: addition or substitution of DMARs/biologics due to inefficacy (79%), adverse event (7%) and others (14%). On multivariate analysis, being younger, having a higher disease activity and initial concomitant treatment with prednisone ≥10mg/day, were associated with a higher methotrexate monotherapy survival (Table 1)

Conclusion: In daily clinical practice, 4 out of 10 patients with early rheumatoid arthritis fail to methotrexate monotherapy, being inefficacy the main reason for discontinuation. Only 7% of patients had to stop treatment due to adverse events. Younger age, higher disease activity and initial combination with prednisone ≥10mg/day were associated with a higher methotrexate monotherapy survival.

Table 1. Cox proportional hazard model
	HR	p-value	95%CI%
Male sex	0.958	0.856	0.605	1.518
Age (years)	0.985	0.018	0.972	0.997
Disease duration (months)	1.008	0.631	0.976	1.041
Baseline DAS28	1.155	0.033	1.012	1.319
Time to first DMAR (months)	0.999	0.724	0.997	1.002
Methotrexate initial dose (mg/week)	1.016	0.585	0.960	1.075
Mean initial dose of prednisone
<10 mg/day	—-	—-	—-	—-
≥10 and <20 mg/day	1.780	0.001	1.254	2.527
≥20 mg/day	3.338	0.008	1.365	8.163

Disclosure: C. A. Waimann, None; M. Landi, None; F. Dal Pra, None; G. Citera, None; M. C. Orozco, None; O. L. Cerda, None; F. Ceccatto, None; S. Paira, None; F. Colombres, None; A. Berman, None; H. Berman, None; A. Secco, None; M. Mamani, None; M. Manzano, None; M. V. Martire, None; F. Caeiro, None; M. Haye Salinas, None; A. J. Alvarellos, None; A. C. Alvarez, None; J. Rosa, None; V. Scaglioni, None; E. R. Soriano, Abbvie; Janssen; UCB; Roche; Bristol Myers Squibb, 2,Abbvie; UCB; Janssen; Roche; Bristol Myers Squibb; Pfizer; Novartis, 8; J. Marcos, None; M. A. García, None; A. Costi, None; A. Martinez, None; O. L. Rillo, None; E. Veloso, None; R. V. Juárez, None; M. E. Crespo, None; A. Quinteros, None; D. Vasquez, None; C. Ledesma, None; G. Salvatierra, None; R. Quintana, None; M. Sacnun, None; M. Abdala, None.

To cite this abstract in AMA style:

Waimann CA, Landi M, Dal Pra F, Citera G, Orozco MC, Cerda OL, Ceccatto F, Paira S, Colombres F, Berman A, Berman H, Secco A, Mamani M, Manzano M, Martire MV, Caeiro F, Haye Salinas M, Alvarellos AJ, Alvarez AC, Rosa J, Scaglioni V, Soriano ER, Marcos J, García MA, Costi A, Martinez A, Rillo OL, Veloso E, Juárez RV, Crespo ME, Quinteros A, Vasquez D, Ledesma C, Salvatierra G, Quintana R, Sacnun M, Abdala M. Drug Survival and Toxicity of Methotrexate Monotherapy in Daily Clinical Practice. Results from an Early Arthritis Clinic [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/drug-survival-and-toxicity-of-methotrexate-monotherapy-in-daily-clinical-practice-results-from-an-early-arthritis-clinic/. Accessed .

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