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

Wiley - Tập 60 Số 2 - Trang 335-344 - 2009
Stanley Cohen1, Tien‐Tsai Cheng2, Vishala Chindalore3, Nemanja Damjanov4, Rubén Burgos‐Vargas5, Patricia DeLora6, Kathleen Zimany6, Helen Travers7, J P Caulfield8
1Metroplex Clinical Research, Dallas, Texas
2Chang Gung Memorial Hospital, Kaohsiung Medical Center, and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
3Pinnacle Research Group, Anniston, Alabama
4Institut za Reumatologiju, Belgrade University School of Medicine, Belgrade, Serbia and Montenegro
5Clínica para el Diagnostico y Tratamiento de las Enfermedades Reumáticas and Hospital General de México, Mexico City, Mexico
6Hoffman-La Roche, Nutley, New Jersey
7Roche Products Ltd, Welwyn Garden City, UK
8Roche Palo Alto LLC Palo Alto California

Tóm tắt

AbstractObjectiveTo 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).MethodsPatients 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.ResultsPatients 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.ConclusionThe present results showed that pamapimod was not as effective as MTX in the treatment of active RA.

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Tài liệu tham khảo

10.2174/1568026054985939

10.1097/00002281-200205000-00013

Salituro FG, 1999, Inhibitors of p38 MAP kinase: therapeutic intervention in cytokine‐mediated diseases, Curr Med Chem, 6, 807, 10.2174/092986730609220401150415

10.1016/S1357-4310(99)01544-0

10.1074/jbc.273.21.12901

10.1016/S0163-7258(99)00008-X

Hale KK, 1999, Differential expression and activation of p38 mitogen‐activated protein kinase α, β, γ, and δ in inflammatory cell lineages, J Immunol, 162, 4246, 10.4049/jimmunol.162.7.4246

10.1002/1529-0131(200011)43:11<2501::AID-ANR18>3.0.CO;2-K

10.1002/art.22080

10.1124/jpet.108.139006

10.1002/art.1780310302

10.1002/art.1780230202

Cella D, 2005, Validation of the Functional Assessment of Chronic Illness Therapy Fatigue Scale relative to other instrumentation in patients with rheumatoid arthritis, J Rheumatol, 32, 811

10.1002/art.1780380602

10.1002/art.1780380107

10.1002/art.1780390105

10.1002/art.1780360601

WeismanM FurstD SchiffM KauffmanR MericaE Martin‐MunleyS et al. A double‐blind placebo‐controlled trial of VX‐745 an oral p38 mitogen activated protein kinase (MAPK) inhibitor in patients with rheumatoid arthritis (RA) [abstract]. Presented at the 2002 annual European Congress of Rheumatology;2002June 12–15; Stockholm Sweden. Abstract FRI0018. URL:http://www.eular.org.

10.1016/j.cgh.2005.11.013

10.1016/j.clpt.2003.11.011

10.1111/j.0906-6705.2003.00045.x

10.1159/000088496

Ding C, 2006, Drug evaluation: VX‐702, a MAP kinase inhibitor for rheumatoid arthritis and acute coronary syndrome, Curr Opin Investig Drugs, 7, 1020

Nikas SN, 2004, SCIO‐469 Scios Inc, Curr Opin Investig Drugs, 5, 1205

10.1002/(SICI)1097-4547(20000601)60:5<623::AID-JNR7>3.0.CO;2-4

10.2174/1568026054985911

10.1038/nbt1358

Clinical Trials.gov. A service of the US National Institutes of Health. URL:http://clinicaltrials.gov.

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Wiley

Tập 60 Số 2

335-344

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