Author's Accepted Manuscript
Effectiveness, tolerability, and safety of subcutaneous methotrexate in early rheumatoid arthritis: A retrospective analysis of realworld data from the St. Gallen cohort Ruediger B. Mueller MD, Johannes von Kempis MD, Sarah R. Haile, Michael H. Schiff MD
www.elsevier.com/locate/semarthrit
PII: DOI: Reference:
S0049-0172(15)00044-X http://dx.doi.org/10.1016/j.semarthrit.2015.02.009 YSARH50902
To appear in:
Seminars in Arthritis and Rheumatism
Cite this article as: Ruediger B. Mueller MD, Johannes von Kempis MD, Sarah R. Haile, Michael H. Schiff MD, Effectiveness, tolerability, and safety of subcutaneous methotrexate in early rheumatoid arthritis: A retrospective analysis of real-world data from the St. Gallen cohort, Seminars in Arthritis and Rheumatism, http://dx.doi.org/10.1016/j.semarthrit.2015.02.009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Effectiveness, tolerability, and safety of subcutaneous methotrexate in early rheumatoid arthritis: A retrospective analysis of real-world data from the St. Gallen cohort
Ruediger B. Mueller, MD,a,* Johannes von Kempis, MD,a,* Sarah R. Haile,b and Michael H. Schiff, MDc a
Division of Rheumatology, Immunology and Rehabilitation, Kantonsspital St. Gallen, St. Gallen, Switzerland b
Division of Biostatistics, Institute for Social and Preventive Medicine, University of Zurich, Switzerland c
University of Colorado, Denver, CO, USA * Both authors contributed equally.
E-mail addresses: Ruediger B. Mueller: [email protected] Johannes von Kempis: [email protected] Sarah Haile: [email protected] Michael H. Schiff: [email protected]
Address correspondence to:
Rüdiger B. Müller, MD Rheumatology, Kantonsspital St. Gallen, Rorschacherstr. 95, 9007 St. Gallen, Switzerland Phone: +41-71-4941138 Fax: 41-71-4946312 E-mail: [email protected]
1
Abstract Introduction: Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment. Recently updated recommendations by the European League Against Rheumatism (EULAR) show MTX as an important part of the first-line strategy in patients with active RA. The study presented here aimed to assess the clinical effectiveness and tolerability of subcutaneous (SC) MTX among patients with RA. Methods: Patients with RA who were naïve at baseline to both conventional and biologic disease-modifying antirheumatic drugs, fulfilled the American College of Rheumatology/EULAR 2010 criteria, and had 1 or more follow-up visits were selected through sequential chart review for analysis of retrospective data. Patients received SC MTX at varying doses (10-25 mg/week). The primary end point was a change in the Disease Activity Score including 28 joints (DAS28); secondary end points included time to employment of the first biologic agent and cumulative MTX doses. Results: Overall, 70 patients were in follow-up for a mean of 1.8 years after initiating SC MTX treatment. During this time, 37 (53%) remained on SC MTX without any biologics (MTX-only) and 33 (47%) required the addition of a biologic therapy (MTX-biol). Biologic therapy was required after a mean ± SD of 387 ± 404 days. Mean weekly MTX doses were 17.4 mg for patients in the MTX-only group and 19.1 mg for patients in the MTX-biol group. Mean baseline DAS28 were similar for patients in the MTX-biol and MTX-only groups (4.9 and 4.7, respectively). Both low disease activity state (LDAS) and remission were achieved by slightly fewer patients in the MTX-biol than MTX-only groups (LDAS, 78.8% vs 81.1%; remission, 69.7% vs 75.7%). Over the full course of the study period, SC MTX was discontinued in 32 patients (46%). Among those who discontinued, the most common reasons were gastrointestinal
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discomfort (n=7), lack of efficacy (n=7), and disease remission (n=3). Severe infections occurred in 3 patients in the MTX-biol group and 3 patients in the MTX-only group. Conclusions: SC MTX is a safe and effective treatment option for patients with RA. SC MTX resulted in high rates of remission and LDAS in early disease, over prolonged periods of time, it, therefore, may extend the time before patients require initiation of biologic therapy.
Keywords: Methotrexate, rheumatoid arthritis, subcutaneous
List of Abbreviations: ACPA: anti-citrullinated protein antibody ACR: American College of Rheumatology AE: adverse event AGREE: Abatacept study to gauge remission and joint damage progression in methotrexatenaïve patients with early erosive rheumatoid arthritis CAMERA: Computer Assisted Management in Early Rheumatoid Arthritis COMET: Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis CRP: C-reactive protein DAS: Disease Activity Score DMARD: disease-modifying antirheumatic drug ESR: erythrocyte sedimentation rate EULAR: European League Against Rheumatism GI: gastrointestinal
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LDAS: low disease activity MTX: methotrexate PREMIER: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment RA: rheumatoid arthritis RF: rheumatoid factor SC: subcutaneous SWEFOT: Analysis of the Swedish Farmacotherapy TEAR: Treatment of Early Aggressive Rheumatoid Arthritis TEMPO: Trial of Etanercept and Methotrexate With Radiographic Patient Outcomes
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1. INTRODUCTION Methotrexate (MTX) has been the cornerstone of treatment for rheumatoid arthritis (RA) for more than 30 years. MTX has the highest 5-year retention rate of all disease-modifying antirheumatic drugs (DMARDs) at approximately 50%, 1-3 and is generally effective in the longterm control of RA (up to 12 years) 4 5. Generally, 13% to 68% of early, untreated patients with RA who are naïve to DMARDs achieve clinical remission (defined as a DAS28 [Disease Activity Score including 28 joints]
Effectiveness, tolerability, and safety of subcutaneous methotrexate in early rheumatoid arthritis: A retrospective analysis of realworld data from the St. Gallen cohort Ruediger B. Mueller MD, Johannes von Kempis MD, Sarah R. Haile, Michael H. Schiff MD
www.elsevier.com/locate/semarthrit
PII: DOI: Reference:
S0049-0172(15)00044-X http://dx.doi.org/10.1016/j.semarthrit.2015.02.009 YSARH50902
To appear in:
Seminars in Arthritis and Rheumatism
Cite this article as: Ruediger B. Mueller MD, Johannes von Kempis MD, Sarah R. Haile, Michael H. Schiff MD, Effectiveness, tolerability, and safety of subcutaneous methotrexate in early rheumatoid arthritis: A retrospective analysis of real-world data from the St. Gallen cohort, Seminars in Arthritis and Rheumatism, http://dx.doi.org/10.1016/j.semarthrit.2015.02.009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Effectiveness, tolerability, and safety of subcutaneous methotrexate in early rheumatoid arthritis: A retrospective analysis of real-world data from the St. Gallen cohort
Ruediger B. Mueller, MD,a,* Johannes von Kempis, MD,a,* Sarah R. Haile,b and Michael H. Schiff, MDc a
Division of Rheumatology, Immunology and Rehabilitation, Kantonsspital St. Gallen, St. Gallen, Switzerland b
Division of Biostatistics, Institute for Social and Preventive Medicine, University of Zurich, Switzerland c
University of Colorado, Denver, CO, USA * Both authors contributed equally.
E-mail addresses: Ruediger B. Mueller: [email protected] Johannes von Kempis: [email protected] Sarah Haile: [email protected] Michael H. Schiff: [email protected]
Address correspondence to:
Rüdiger B. Müller, MD Rheumatology, Kantonsspital St. Gallen, Rorschacherstr. 95, 9007 St. Gallen, Switzerland Phone: +41-71-4941138 Fax: 41-71-4946312 E-mail: [email protected]
1
Abstract Introduction: Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment. Recently updated recommendations by the European League Against Rheumatism (EULAR) show MTX as an important part of the first-line strategy in patients with active RA. The study presented here aimed to assess the clinical effectiveness and tolerability of subcutaneous (SC) MTX among patients with RA. Methods: Patients with RA who were naïve at baseline to both conventional and biologic disease-modifying antirheumatic drugs, fulfilled the American College of Rheumatology/EULAR 2010 criteria, and had 1 or more follow-up visits were selected through sequential chart review for analysis of retrospective data. Patients received SC MTX at varying doses (10-25 mg/week). The primary end point was a change in the Disease Activity Score including 28 joints (DAS28); secondary end points included time to employment of the first biologic agent and cumulative MTX doses. Results: Overall, 70 patients were in follow-up for a mean of 1.8 years after initiating SC MTX treatment. During this time, 37 (53%) remained on SC MTX without any biologics (MTX-only) and 33 (47%) required the addition of a biologic therapy (MTX-biol). Biologic therapy was required after a mean ± SD of 387 ± 404 days. Mean weekly MTX doses were 17.4 mg for patients in the MTX-only group and 19.1 mg for patients in the MTX-biol group. Mean baseline DAS28 were similar for patients in the MTX-biol and MTX-only groups (4.9 and 4.7, respectively). Both low disease activity state (LDAS) and remission were achieved by slightly fewer patients in the MTX-biol than MTX-only groups (LDAS, 78.8% vs 81.1%; remission, 69.7% vs 75.7%). Over the full course of the study period, SC MTX was discontinued in 32 patients (46%). Among those who discontinued, the most common reasons were gastrointestinal
2
discomfort (n=7), lack of efficacy (n=7), and disease remission (n=3). Severe infections occurred in 3 patients in the MTX-biol group and 3 patients in the MTX-only group. Conclusions: SC MTX is a safe and effective treatment option for patients with RA. SC MTX resulted in high rates of remission and LDAS in early disease, over prolonged periods of time, it, therefore, may extend the time before patients require initiation of biologic therapy.
Keywords: Methotrexate, rheumatoid arthritis, subcutaneous
List of Abbreviations: ACPA: anti-citrullinated protein antibody ACR: American College of Rheumatology AE: adverse event AGREE: Abatacept study to gauge remission and joint damage progression in methotrexatenaïve patients with early erosive rheumatoid arthritis CAMERA: Computer Assisted Management in Early Rheumatoid Arthritis COMET: Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis CRP: C-reactive protein DAS: Disease Activity Score DMARD: disease-modifying antirheumatic drug ESR: erythrocyte sedimentation rate EULAR: European League Against Rheumatism GI: gastrointestinal
3
LDAS: low disease activity MTX: methotrexate PREMIER: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment RA: rheumatoid arthritis RF: rheumatoid factor SC: subcutaneous SWEFOT: Analysis of the Swedish Farmacotherapy TEAR: Treatment of Early Aggressive Rheumatoid Arthritis TEMPO: Trial of Etanercept and Methotrexate With Radiographic Patient Outcomes
4
1. INTRODUCTION Methotrexate (MTX) has been the cornerstone of treatment for rheumatoid arthritis (RA) for more than 30 years. MTX has the highest 5-year retention rate of all disease-modifying antirheumatic drugs (DMARDs) at approximately 50%, 1-3 and is generally effective in the longterm control of RA (up to 12 years) 4 5. Generally, 13% to 68% of early, untreated patients with RA who are naïve to DMARDs achieve clinical remission (defined as a DAS28 [Disease Activity Score including 28 joints]
