The role of DMARDs in reducing the immunogenicity of TNF inhibitors in chronic inflammatory diseases

Jani, Meghna; Barton, Anne; Griffiths, C.E.M.; Chinoy, Hector

doi:10.1093/rheumatology/ket260

Cited by 183 publications

(120 citation statements)

References 64 publications

(78 reference statements)

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“…For the treatment of arthritis in JIA, it is suggested that ADA combined with MTX has a higher efficacy than without, as has been demonstrated in the phase III study (29). It is further known that MTX decreases the antibody production against ADA and therefore magnifies the efficacy of ADA also (30).…”

mentioning

confidence: 99%

Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry

Foeldvari

Becker

Horneff

2015

Arthritis Care & Research

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ObjectiveUveitis is a major extraarticular quality of life–restricting manifestation of juvenile idiopathic arthritis (JIA). The aim of the study is to describe the occurrence of uveitis in JIA patients receiving tumor necrosis factor inhibitors or methotrexate (MTX).MethodsPatients’ characteristics, treatment, and the reported first occurrence of uveitis as an adverse event were searched in the Biologics in Pediatric Rheumatology Registry. The rates per exposed patients, exposure time, and time until event were calculated.ResultsUveitis was reported as an adverse event in 75 of 3,467 patients; 51 of 2,844 patients were receiving MTX, 37 of 1,700 patients were receiving etanercept, and 13 of 364 patients were receiving adalimumab. Patients with uveitis were younger (mean ± SD age 4.6 ± 4.2 versus 7.4 ± 4.5 years; P < 0.0001), more likely to be antinuclear antibody positive (69% versus 43%; odds ratio [OR] 2.7, P < 0.0001), and had extended oligoarticular JIA (OR 2.2, P = 0.0005). Patients with a uveitis diagnosis before starting treatment more often had a uveitis event (n = 28, 8.4%; OR 8.5, P < 0.0001), and more often received adalimumab (OR 2.15 [95% confidence interval 1.58–2.94], P < 0.0001). In 16 patients, a new uveitis event occurred: 11 while taking MTX (3.2 per 1,000 patient‐years), 2 while taking etanercept monotherapy (1.9 per 1,000 patient‐years), and 3 while taking etanercept and MTX combination (0.9 per 1,000 patient‐years). A new uveitis event occurred early in the disease course after a median disease duration of 1.5 years (interquartile range [IQR] 1.3–3.8) while taking etanercept and 1.8 years (IQR 1.8–2.1) for the MTX cohort. A recurrent uveitis event was reported after a disease duration of 7.6 years (IQR 4.3–10.0) in the etanercept cohort and 4.8 years (IQR 1.0–5.8) in the MTX cohort. Univariate analysis showed that MTX, but not etanercept or adalimumab, led to a lower rate of uveitis.ConclusionPatients with a history of uveitis had higher risks for uveitis events while taking both etanercept and adalimumab. Methotrexate turned out to be protective. Few patients developed a first uveitis event while taking etanercept, while the rate is comparable to that with MTX. Uveitis may not be attributed to be an adverse drug reaction to etanercept.

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mentioning

confidence: 99%

Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry

Foeldvari

Becker

Horneff

2015

Arthritis Care & Research

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“…MTX is recommended as a first-line treatment in patients with active RA 14,15 , and because of its additive efficacy benefits and its reductions in immunogenicity, is typically used in combination with biologics 16 . Although several systematic or comprehensive reviews have evaluated adherence to DMARD in general 7,17,18 , only 1 systematic study, to our knowledge, has specifically evaluated MTX adherence (but not persistence) in patients with RA 13 .…”

mentioning

confidence: 99%

Adherence and Persistence with Methotrexate in Rheumatoid Arthritis: A Systematic Review

Curtis

Bykerk

Aassi³

et al. 2016

J Rheumatol

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Objective.Medication adherence in patients with rheumatoid arthritis (RA) is typically suboptimal. Nonadherence has been associated with symptom worsening and increased disability. We systematically reviewed published clinical studies to evaluate methotrexate (MTX) adherence and persistence, factors associated with MTX adherence and persistence, and the effect of MTX nonadherence on clinical outcomes in RA.Methods.MEDLINE and Embase were systematically searched (inception to February 2016) using relevant keywords. Observational or interventional clinical studies in patients with RA that specifically reported adherence to or persistence with MTX were included. Data were extracted using a predesigned, standardized template that included study design, patient demographics, and relevant outcomes. Main outcomes were MTX adherence and persistence rates in patients with RA treated with MTX and factors associated with MTX adherence and persistence.Results.Of 365 references screened, 31 articles met inclusion criteria and another 10 were identified from searching reference lists. Estimates of MTX adherence varied from study to study because of heterogeneity in patient populations, duration of followup, definitions of adherence, and methods of assessment. Rates of MTX persistence ranged from 50% to 94% at 1 year and 25% to 79% at 5 years. No clear trends were identified in factors that influence MTX adherence and persistence. Two studies suggested that MTX adherence was associated with superior clinical outcomes.Conclusion.MTX adherence and persistence are highly variable in patients with RA. Research is necessary to determine the effect of nonadherence on health outcomes and to identify independent predictors of nonadherence to inform evidence-based interventions.

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“…These occur when the patient mounts an immune response to the drug itself, and may result in reduced treatment efficacy and infusion reactions. 33 Co-administration of methotrexate or another DMARD appears to reduce ADA development, 34 hence many children may be prescribed a DMARD and a bDMARD simultaneously.…”

Section: Cd20 (B Cells) IV Infusionmentioning

confidence: 99%

Modern management of juvenile idiopathic arthritis

James¹,

Wedderburn²

2016

Prescriber

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The role of DMARDs in reducing the immunogenicity of TNF inhibitors in chronic inflammatory diseases

Cited by 183 publications

References 64 publications

Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry

Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry

Adherence and Persistence with Methotrexate in Rheumatoid Arthritis: A Systematic Review

Modern management of juvenile idiopathic arthritis

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