Patient Maintenance Therapy With Subcutaneous Methotrexate Weekly - - PowerPoint PPT Presentation

Assessing Rheumatoid Arthritis Patient Maintenance Therapy With Subcutaneous Methotrexate Weekly Versus Monthly

Karim Richard Masri, MD Rheumatology Fellow July 25, 2014

Background

• Rheumatoid arthritis (RA):

– Chronic, systemic autoimmune inflammatory disease – Typically involves small joints symmetrically

• Extra-articular abnormalities include:

– Cardiopulmonary – Neurologic – Hematologic

• Untreated RA results in destructive debilitating arthropathy

Methotrexate (MTX)

• MTX is first drug of choice for RA
• Disrupts DNA synthesis, hindering cell replication
• Has a pro-adenosine mechanism that carries anti-

inflammatory properties

• SubQ MTX

– Is an injection – like insulin – Compared with oral

• Has higher bioavailability
• Carries less gastrointestinal side effects
• Is cheaper

• Patients are responsible for their treatment:

– Evaluation and follow up with their rheumatologist – Adhering to their treatment

• Treatment is tried over 3 months prior to

medication augmentation or switching

• Composite scores measure disease activity

Clinical Disease Activity Index (CDAI)

• A composite score that takes into account:

– Tender joints – Swollen joints – Patient global assessment – Physician global assessment

CDAI <= 2.8: Remission CDAI > 2.8 and <= 10: Low Disease Activity CDAI > 10 and <= 22: Moderate Disease Activity CDAI > 22: High Disease Activity

Hypothesis

• Monthly high-dose subQ MTX of 50 mg is non-

inferior in maintaining low disease activity (CDAI 2.9-10) compared to weekly traditional subQ dose of 25 mg

Study Population

• 620 patients from the Johns Hopkins Arthritis Center:

– ≥ 30 years with newly diagnosed or previously diagnosed RA – Low disease activity to high disease activity (CDAI >2.8) – Exclusion criteria are:

• Chronic kidney disease
• Biologic use (anti-TNF, anti-IL-6, anti-IL-1, anti-CD20, or JAK inhibitors)
• Liver disease
• Daily alcohol use
• Pneumonitis
• Malignancy

Study Design

• Double-blinded randomized non-inferiority trial
• Folic acid 1 mg will also be administered daily in both arms
• Follow-up over 3 months

N=620 N=310 50 mg MTX monthly + weekly placebo N=310 25 mg MTX weekly

Patient Stratum

• Data collection will be done by office visit

50 mg MTX monthly 25 mg MTX weekly Age (n=620) Sex (F) Smoking Serologic Markers (RF and anti-CCP) Baseline CDAI Baseline ESR (mm/hr) Baseline CRP (mg/dL) DAS28ESR

Tolerance and Adherence Measures

• Serially measured labs on days 0, 14, 30, 45,

60, 75, and 90

– Inflammatory marker (ESR and CRP) – Kidney and liver function test – Complete blood count – Serum methotrexate levels

Monthly Physician Follow up

• To assess for medication tolerance and clinical

response, using composite measures of CDAI

• CDAI = TJ + SJ + PGA + EGA

CDAI <= 2.8: Remission CDAI > 2.8 and <= 10: Low Disease Activity CDAI > 10 and <= 22: Moderate Disease Activity CDAI > 22: High Disease Activity

Analytical Strategy

• The significance level (alfa) of 5%
• The power is 80% to test the hypothesis
• The non-inferiority limit is 10%
• Logistic Regression analysis

Outcomes

• Primary outcome

– CDAI consistent with remission and low disease activity (CDAI ≤10)

• Secondary outcomes

– Change of CDAI score – Clinical and laboratory tolerance – Adherence (MTX level)

Study Limitations

• Sample size – too large
• Injection burden
• Patient drop out

Significance

• If high-dose monthly methotrexate (MTX) is non-

inferior with good tolerance and adherence, it may become a new dosing regimen for methotrexate in rheumatoid arthritis patients

Acknowledgements

• Ashley Altman, MD
• Jemi Badamas, MD
• Nisha Gilotra, MD
• Michelle Estrella, MD
• Corinne Keet, MD