Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis

Authors

  • Stanley B. Cohen,

    Corresponding author
    1. Metroplex Clinical Research, Dallas, Texas
    • Metroplex Clinical Research Center, 5939 Harry Hines Boulevard, Suite 441, Dallas, TX 75235
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    • Dr. Cohen has served as a clinical investigator and research consultant for Genentech, Biogen Idec, Roche, Procter & Gamble, Pfizer, Centocor, Amgen, Scios, and Wyeth-Ayerst, and has received consulting and/or speaking fees from these companies (less than $10,000 each).

  • Tien-Tsai Cheng,

    1. Chang Gung Memorial Hospital–Kaohsiung Medical Center, and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Vishala Chindalore,

    1. Pinnacle Research Group, Anniston, Alabama
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    • Dr. Chindalore has received speaking fees from Roche, Pfizer, and GlaxoSmithKline (less than $10,000 each).

  • Nemanja Damjanov,

    1. Institut za Reumatologiju, Belgrade University School of Medicine, Belgrade, Serbia and Montenegro
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  • Ruben Burgos-Vargas,

    1. Clínica para el Diagnostico y Tratamiento de las Enfermedades Reumáticas and Hospital General de México, Mexico City, Mexico
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    • Dr. Burgos-Vargas has received consulting fees, speaking fees, and/or honoraria from Roche, Schering-Plough, Wyeth, and Abbott (less than $10,000 each).

  • Patricia DeLora,

    1. Hoffman-La Roche, Nutley, New Jersey
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    • Ms DeLora owns stock or stock options in Hoffman-La Roche.

  • Kathleen Zimany,

    1. Hoffman-La Roche, Nutley, New Jersey
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  • Helen Travers,

    1. Roche Products Ltd., Welwyn Garden City, UK
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  • John P. Caulfield

    1. Roche Palo Alto, LLC, Palo Alto, California
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    • Dr. Caulfield owns stock or stock options in Roche.


  • ClinicalTrials.gov identifier: NCT00303563.

Abstract

Objective

To determine the efficacy and safety of pamapimod (a selective inhibitor of the α-isoform of p38 MAP kinase) as monotherapy in comparison with methotrexate (MTX) treatment in adult patients with active rheumatoid arthritis (RA).

Methods

Patients were randomly assigned to 1 of 4 treatment groups and received 12 weeks of double-blind treatment. One group received MTX (7.5 mg/week with planned escalation to 20 mg/week), and 3 groups received pamapimod (50, 150, or 300 mg) once daily. The primary efficacy end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks. Secondary end points included ACR50 and ACR70 responses, change from baseline in the Disease Activity Score in 28 joints (DAS28), categorical analyses of DAS28/European League Against Rheumatism response, and change from baseline in each parameter of the ACR core set of measures. Safety monitoring included recording of adverse events (AEs), laboratory testing, immunology assessments, administration of electrocardiograms, and assessment of vital signs.

Results

Patients assigned to receive MTX and pamapimod had similar demographics and baseline characteristics. At week 12, fewer patients taking pamapimod had an ACR20 response (23%, 18%, and 31% in the 50-, 150-, and 300-mg groups, respectively) compared with patients taking MTX (45%). Secondary efficacy end points showed a similar pattern. AEs were typically characterized as mild and included infections, skin disorders, and dizziness. Pamapimod was generally well tolerated, but the 300-mg dose appeared to be more toxic than either the 2 lower doses or MTX.

Conclusion

The present results showed that pamapimod was not as effective as MTX in the treatment of active RA.

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