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 N=620 N=310 N=310 50 mg MTX monthly 25 mg MTX weekly + weekly placebo • Folic acid 1 mg will also be administered daily in both arms • Follow-up over 3 months

Patient Stratum 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 • Data collection will be done by office visit

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 <= 2.8: Remission CDAI > 2.8 and <= 10: Low Disease Activity CDAI > 10 and <= 22: Moderate Disease Activity CDAI > 22: High Disease Activity • CDAI = TJ + SJ + PGA + EGA

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