1323 Magnano, et al: TNF in hand OA Personal non-commercial use only. The Journal of Rheumatology Copyright © 2007. All rights reserved. A Pilot Study of Tumor Necrosis Factor Inhibition in Erosive/Inflammatory Osteoarthritis of the Hands MOLLYD.MAGNANO,ELIZAF.CHAKRAVARTY,CORRIEBROUDY,LORINDACHUNG,ARIELLAKELMAN, JENNIFERHILLYGUS,andMARKC.GENOVESE ABSTRACT. Objective. To determine if anti-tumor necrosis factor (TNF) therapy (adalimumab) can safely improve symptoms of erosive/inflammatory osteoarthritis (EOA). Methods. Thiswasanopen-labelpilottrialin12patientswithEOA.Patients>45yearsoldwithEOA of the hands defined by ≥ 2 tender and ≥ 2 swollen joints (distal interphalangeal, proximal interpha- langeal, first carpometacarpal) despite nonsteroidal antiinflammatory drug therapy were eligible. Patientswereexcludedforautoimmunearthritis,recentdiseasemodifyingantirheumaticdruguse,prior use of anti-TNF therapy, infection, malignancy, or poorly controlled medical conditions.All patients receivedadalimumab40mgeveryotherweekfor12weeks.Safetywasassessed4weeksafterthefinal dose. Primary endpoints included safety andAmerican College of Rheumatology (ACR) response. Results. Patientswerepredominantlyfemalewithameanageof60yearsand12yearsofarthritis.All patients completed the study and safety followup.Adverse events were mild without necessitating dis- continuation of study drug. After 12 weeks, there was a statistically significant improvement in the number of swollen joints compared to baseline (p < 0.01). One patient achieved an ACR20 response and 42% achieved an OMERACT-OARSI response.Although we detected no statistically significant improvement in the number of tender joints, grip strength, disability, pain, or global disease assess- ments, trends suggested modest improvement in all efficacy measures. Conclusion. Thissmallopen-labelstudyofpatientswithEOAdemonstratedthatadalimumabwaswell tolerated. Treatment with adalimumab for 3 months did not significantly improve the signs and symp- toms of EOA and most patients did not achieve an ACR20. Trends suggested improvement and indi- vidualpatientshadsomebenefit.Factorslimitinginterpretationofthisstudyincludethelackofacon- trol group, outcomes chosen, number of patients treated, and the duration of treatment. (First Release May 15 2007; J Rheumatol 2007;34:1323–7) Key Indexing Terms: OSTEOARTHRITIS TUMORNECROSISFACTOR TREATMENT CYTOKINE From the Division of Immunology and Rheumatology, Stanford University, Palo Alto, California, USA. Supported by Abbott Pharmaceuticals and grant 5 M01 RR000070 from the National Center for Research Resources, National Institutes of Health. M.D. Magnano, MD, Postdoctoral Fellow; E.F. Chakravarty, MD, Assistant Professor; C. Broudy, MD, Postdoctoral Fellow; L. Chung, MD, Assistant Professor; A. Kelman, MD, Adjunct Clinical Professor, Stanford University, Medical Director, Genentech Inc.; J. Hillygus, Research Assistant; M. Genovese, Associate Professor of Medicine, Division of Immunology and Rheumatology, Stanford University. Address reprint requests to Dr. M. Genovese, Division of Immunology and Rheumatology, Stanford University, 1000 Welch Road, Suite 203, Palo Alto, CA 94304. E-mail: genovese@stanford.edu Accepted for publication February 26, 2007. Osteoarthritis (OA) is a heterogeneous group of conditions with defective integrity of articular cartilage and changes in underlyingbone.ThepathogenesisofOAismultifactorialand involves a complex interplay of genetic, metabolic, biochem- ical, and biomechanical factors with variable components of inflammation. A subset of patients with OA develop an inflammatory and erosive form of the disease. Erosive osteoarthritis (EOA) is clinically recognized in peri- menopausalfemalepatientswhodevelopsynovitisinthedis- tal and proximal interphalangeal (DIP, PIP) joints of the hands.TheclassicradiologicalchangesofEOAarecharacter- ized by a combination of bony proliferation and central ero- sionsresultingintheclassic“gull-wingdeformity.”Inclinical studies, the diagnosis of EOA is accepted only for patients meeting American College of Rheumatology (ACR) clinical criteria for OA of the hand and showing radiographic aspects of articular surface erosions 1 . Agrowingbodyofevidencesupportsthetheorythataber- rant cytokine biology is important to the pathophysiology of OA.MorphologicalchangesobservedinOAincludecartilage erosion as well as variable degrees of synovial inflammation. Cartilagefromequineosteoarthritickneesdemonstrateslevels of interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and numerous matrix metalloproteinases (MMP) above those foundinnormaljoints 2 .Thiscytokinemilieusignalssynovio- cytes and chondrocytes to express metalloproteinases that destroy the structural integrity of synovial cartilage 3 . In response to this inflammatory environment, chondrocytes show a diminished capacity to self-repair in response to growth factors, resulting in irreversible cartilage damage 4 . www.jrheum.org Downloaded on July 1, 2022 from