INT182320

Context Info Confidence 0.18 First Reported 2005 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 14 Total Number 14 Disease Relevance 8.50 Pain Relevance 7.65

mitochondrion (MTX1)

Anatomy Link Frequency liver 1 superior 1 MTX1 (Homo sapiens)

Pain Link Frequency Relevance Heat methotrexate 440 100.00 rheumatoid arthritis 574 99.82 Adalimumab 140 99.80 Etanercept 136 99.80 Infliximab 93 99.80 Pain 8 98.48 Leflunomide 11 95.92 antagonist 38 93.36 Arthritis 218 93.24 headache 12 89.12

Disease Link Frequency Relevance Heat Rheumatoid Arthritis 578 99.82 Disease 233 95.88 Demyelinating Disease 13 94.12 Seronegative Spondarthritis 133 94.00 Juvenile Chronic Polyarthritis 90 93.24 Mycobacterial Infection 88 93.12 Hypersensitivity 8 93.12 Arthritis 75 92.24 Arthropathy 96 92.04 Malignant Neoplastic Disease 20 92.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Both primary endpoints were met.24 Both 50 mg GLM + MTX and 100 mg GLM + MTX were comparable in efficacy and achieved statistical significance for all secondary endpoints at 24 weeks including ACR50, ACR70, DAS28 (using CRP) responders, and DAS28 (CRP) remission.24 Results from this trial confirm the efficacy of GLM in patients with active RA despite MTX therapy that was observed in the phase II trial,20 and demonstrate that 50 mg GLM or 100 mg GLM administered every four weeks in combination with MTX significantly reduces signs and symptoms and improves physical function in patients with RA.

MTX Binding (combination) of associated with rheumatoid arthritis and methotrexate

1) Confidence 0.18 Published 2010 Journal Core evidence Section Body Doc Link PMC2899784 Disease Relevance 0.39 Pain Relevance 0.49

For all endpoints, combination therapy was superior to both MTX and adalimumab monotherapy (Table 2).

MTX Binding (superior) of in superior associated with adalimumab and methotrexate

2) Confidence 0.17 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1936294 Disease Relevance 0.44 Pain Relevance 1.11

10 mm/hr) despite treatment with MTX ?

MTX Binding (treatment) of associated with methotrexate

3) Confidence 0.16 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1936291 Disease Relevance 0.40 Pain Relevance 1.19

TCZ has been approved in the US as monotherapy and in combination with MTX for the treatment of moderate to severely active RA in patients who have had an inadequate response to one or more TNF-?

MTX Binding (combination) of associated with rheumatoid arthritis and methotrexate

4) Confidence 0.16 Published 2010 Journal Drug Design, Development and Therapy Section Body Doc Link PMC2990387 Disease Relevance 0.97 Pain Relevance 0.22

Furthermore, since anti-tocilizumab antibodies are not detected without use of MTX, the combination with MTX is not required to suppress the emergence of anti-tocilizumab antibodies as long as 8 mg/kg of tocilizumab is used.

MTX Binding (combination) of associated with methotrexate

5) Confidence 0.15 Published 2008 Journal Mod Rheumatol Section Body Doc Link PMC2638601 Disease Relevance 0.28 Pain Relevance 0.52

Group 1 included patients receiving MTX (n = 18), group 2 included patients treated with combination of MTX and TNF-?

MTX Binding (combination) of associated with methotrexate

6) Confidence 0.15 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065333 Disease Relevance 0.59 Pain Relevance 0.34

Patients treated with combination of MTX and TNF-?

MTX Binding (combination) of associated with methotrexate

7) Confidence 0.15 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065333 Disease Relevance 0.34 Pain Relevance 0.31

were used in 47 patients (42 patients in combination with MTX, three patients in combination with azathioprine, one patient in combination with cyklosporine, and the remaining patient in combination with cyclophosphamide).

MTX Binding (combination) of associated with methotrexate

8) Confidence 0.13 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065333 Disease Relevance 0.39 Pain Relevance 0.53

Combined biologic therapy with MTX and Etanercept was necessary for 12.5% of patients.

MTX Binding (therapy) of associated with etanercept and methotrexate

9) Confidence 0.13 Published 2010 Journal Pediatr Rheumatol Online J Section Body Doc Link PMC2964715 Disease Relevance 1.69 Pain Relevance 0.72

In this study tocilizumab in monotherapy for 24 weeks significantly improved signs and symptoms and was well tolerated in patients who had active RA despite receiving MTX.

MTX Binding (receiving) of associated with rheumatoid arthritis and methotrexate

10) Confidence 0.11 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727785 Disease Relevance 0.28 Pain Relevance 0.45

From these findings, it can be anticipated that monotherapy with tocilizumab 8 mg/ kg will yield equivalent clinical efficacy to TNF inhibitor in combination with MTX.

MTX Binding (combination) of associated with methotrexate

11) Confidence 0.11 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727785 Disease Relevance 0.24 Pain Relevance 0.40

Patients with intolerance to MTX despite the association with folic acid could also be included.

MTX Binding (association) of associated with methotrexate

12) Confidence 0.07 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911915 Disease Relevance 0.39 Pain Relevance 0.35

These studies have shown clinical response rates of 40% to 60% in patients treated with a combination of MTX and infliximab.

MTX Binding (combination) of associated with infliximab and methotrexate

13) Confidence 0.07 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2911915 Disease Relevance 1.58 Pain Relevance 0.83

Monitoring of serum liver enzymes is recommended during TCZ treatment, especially when the latter is combined with MTX.

MTX Binding (combined) of in liver associated with methotrexate

14) Confidence 0.04 Published 2009 Journal Mod Rheumatol Section Body Doc Link PMC2720589 Disease Relevance 0.53 Pain Relevance 0.20

General Comments

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