Ankylosing Spondylitis

Phase 3 Data Show New Anti-TNF, Golimumab, Significantly Improved Arthritis, Skin and Nail Manifestations in Patients with Psoriatic Arthritis

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Golimumab, Centocor Inc. and Schering-Plough Corporation's next-generation human anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, is currently in the most comprehensive Phase 3 development program to date for an anti-TNF- alpha biologic therapy. With ongoing studies for the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, golimumab is being studied as a monthly SC injection and an every twelve-week intravenous (IV) infusion (approximately 30-minutes) therapy.

"The availability of treatments that target TNF-alpha have dramatically changed rheumatologists' approach to the management of psoriatic arthritis, a potentially disabling inflammatory disease," said Arthur Kavanaugh, MD, Professor of Medicine, University of California, San Diego, School of Medicine, and lead study investigator. "These findings show golimumab to be promising in the treatment of multiple facets of the disease, namely the joints and skin, and support the utility of this anti-TNF-alpha treatment."

Joint and Psoriatic Improvements

Initial improvements as measured by ACR 20 at week 14 persisted through six months. At week 24, 52 percent and 61 percent of patients receiving golimumab 50 mg and golimumab 100 mg, respectively, achieved ACR 20, compared with 12 percent of patients receiving placebo (P < 0.001). Significant improvements were observed in ACR 50 and ACR 70 measures at the same time points. At week 14, 30 percent and 28 percent of patients receiving golimumab 50 mg and golimumab 100 mg, respectively, achieved ACR 50, compared with 2 percent of patients receiving placebo (P < 0.001). At week 24, the results persisted with 32 percent and 38 percent of patients receiving golimumab 50 mg and golimumab 100 mg, respectively, achieving ACR 50 as compared with four percent of patients receiving placebo (P < 0.001). ACR 70, a more stringent response criterion, was achieved at week 14 by 12 percent of patients receiving golimumab 50 mg and 17 percent receiving golimumab 100 mg, compared with 1 percent of patients receiving placebo (P < 0.001). At week 24, 19 percent of patients receiving golimumab 50 mg and 21 percent of patients receiving golimumab 100 mg achieved ACR 70 as compared with 1 percent of patients receiving placebo (P < 0.001).

Patients receiving both doses of golimumab also experienced improvements in enthesitis and dactylitis, two common disease manifestations causing pain and swelling. Enthesitis, an inflammation of a tendon, ligament or joint capsule insertion to the bone and dactylitis, a swelling of digits in the hands or feet, are estimated to affect more than one-third of people with psoriatic arthritis. At baseline, 78 percent (placebo group), 75 percent (golimumab 50 mg group) and 79 percent (golimumab 100 mg group) of study subjects presented with enthesitis (at least one tender body enthesitis site) as measured by the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) index modified for Psoriatic Arthritis; 34 percent (placebo group), 34 percent (golimumab 50 mg group) and 34 percent (golimumab 100 mg group) of subjects presented with dactylitis at baseline.

Both golimumab doses were significantly better than placebo in improvement of enthesitis as measured by percent change in the psoriatic arthritis modified MASES Index.

At week 14, the mean improvement in enthesitis was 44 percent among patients receiving golimumab 50 mg and 33 percent among patients receiving golimumab 100 mg, compared with a 19 percent worsening in patients receiving placebo (P < 0.001). At week 24, the mean improvements in enthesitis were 46 percent for patients receiving golimumab 50 mg and 52 percent among patients receiving golimumab 100 mg, compared with a 13 percent worsening in placebo patients (P < 0.001). The golimumab 100 mg dose significantly improved dactylitis measured by percent change in dactylitis score compared with placebo at week 14 (66 percent versus 5 percent; P =3D 0.009) and at week 24 (82 percent versus 28 percent; P < 0.001). There was a trend towards improvement in dactylitis for 50 mg golimumab dose at week 14 and 24 but the comparisons with placebo did not reach statistical significance.

In addition to improvements in joint symptoms, a substantial proportion of golimumab-treated patients experienced significant improvement in skin manifestations of the disease. Among a subset of the study population with at least three percent of body surface area involved by psoriasis at baseline, 40 percent and 58 percent of patients receiving golimumab 50 mg and golimumab 100 mg, respectively, achieved PASI 75 at week 14, compared with 3 percent of patients receiving placebo (P < 0.001). At week 24, PASI 75 responses improved to 56 percent (golimumab 50 mg) and 66 percent (golimumab 100 mg), compared with 1 percent of placebo patients (P < 0.001). In additional analyses, patients receiving golimumab 50 mg and golimumab 100 also experienced improvements in nail psoriasis as measured by NAPSI and these improvements were sustained over time.

"These Phase 3 data show that once monthly subcutaneous administrations of golimumab 50 mg and golimumab 100 mg significantly improved articular and psoriatic manifestations in patients with psoriatic arthritis," said Jerome A. Boscia, MD, senior vice president, Clinical Research and Development, Centocor, Inc. "We are encouraged by these results and believe golimumab holds great promise as a new anti-TNF-alpha therapy for physicians and patients in need of additional therapeutic options."

Disease Activity and Physical Function Improvements

The majority of golimumab-treated patients in the study were classified as good or moderate responders as measured by the Disease Activity Score 28 (DAS28), which measures tender and swollen joints and overall disease activity including measurement of serum C-reactive protein (CRP) levels. After 14 weeks of treatment, 66 percent of patients receiving golimumab 50 mg were DAS28 responders, as were 67 percent of patients receiving the 100 mg dose, compared with 24 percent of patients receiving placebo (P < 0.001). At week 24, 64 percent and 78 percent of patients receiving golimumab 50 mg and 100 mg, respectively, were DAS28 responders, compared with 24 percent of patients receiving placebo (P < 0.001).

Patients receiving golimumab in the study also experienced significant improvements in physical function, as measured by the Health Assessment Questionnaire (HAQ). At week 14, patients receiving golimumab 50 mg experienced a mean improvement of 0.31 and patients receiving golimumab 100 mg experienced a mean improvement of 0.38 in HAQ score, compared with an improvement of only 0.04 among placebo patients (P < 0.001). At week 24, the improvements were 0.33 and 0.39 in the respective treatment groups, compared with worsening in HAQ score of -0.01 among patients receiving placebo (P < 0.001). HAQ assesses the degree of difficulty a patient has in accomplishing tasks in eight functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping and other activities of daily living). An improvement in HAQ of at least 0.3 indicates clinically meaningful improvement in physical function.

Keywords: Ankylosing Spondylitis, Anticancer Therapy, Biotechnology, Clinical Trial Research, Dermatology, Immunotherapy, Medical Device, Monoclonal Antibodies, Monoclonal Antibody, Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, Rheumatology, Skin Manifestations, Therapy, Treatment, Centocor Inc.

This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.