August 3rd, 2008
Marked by pain, swelling, stiffness, and progressive destruction of multiple joints, rheumatoid arthritis (RA) is a highly disabling, chronic inflammatory disease. Complex immune mechanisms contribute to the pathology of RA. Currently, the standard drugs prescribed for RA—pain-relieving analgesics, cell-depleting cytotoxic agents, and disease-modifying antirheumatic drugs (DMARDs)—suppress the immune system nonspecifically. While often effective at controlling the symptoms of RA, these therapies are associated with significant side effects, from insomnia to vomiting and mouth ulcers.
Immune tolerance, a state of immunologic response where the immune system does not attack antibody-generating antigens, has posed intriguing possibilities for the treatment of autoimmune diseases. In RA, type II collagen (CII) of the articular cartilage is one of the candidate autoantigens; some RA patients demonstrate immunity against CII. When administered orally, chicken type II collagen (CCII) has worked to reduce inflammation, cartilage degradation, and inflammatory cell infiltration in the knee joints of rats and mice with collagen-induced arthritis.
Motivated by the experiments with rodents, a team of researchers in China conducted a randomized, double-blind, controlled trial to evaluate the therapeutic potential of CCII for humans with RA. The results, presented in the July 2008 issue of Arthritis Care & Research, affirm chicken type II collagen as not only effective in the treatment of RA, but also well tolerated and safe. CCII was found to have a lower incidence of adverse events than the most popular DMARD, methotrexate (MTX).
Conducted at 4 medical research centers over a course of 24 weeks, the study focused on 236 patients who met the American College of Rheumatology (ACR) criteria for the diagnosis of RA and had active disease duration for at least 6 months but not longer than 24 months. The mean age of the subjects was 47 years and the majority, over 85 percent, was female. Patients were randomly assigned to receive either CCII, at a dosage level of 1 milligram per day, or MTX, 10 milligrams per week. Throughout the study, all patients and investigators were blinded to the treatment regimens.
At baseline and again at 12, 18, and 24 weeks, every patient was clinically evaluated for pain, morning stiffness, swollen and tender joint counts, functional status, and overall health. To rate the results and document improvements, researchers used standard tools such as visual analog scales and the Health Assessment Questionnaire (HAQ). At each visit, patients were asked whether they had noticed any side effects since their last visit. To monitor patient safety, a complete blood cell count, urinalysis, and tests of critical laboratory variables were conducted at entry, 12 weeks, and 24 weeks.
Patients in both the CCII and MTX group experienced significant decreases in pain, morning stiffness, tender joint count, and swollen joint count, as well as significant gains in patient and physician assessments of general health and functional capacity. At 12 weeks, 30 percent of patients in the CCII group and 44 percent of patients in the MTX group met the ACR criteria for 20 percent improvement in RA symptoms, and 19 percent and 31 percent, respectively, met the ACR 50 percent improvement criteria. At 24 weeks, 69 percent of the CII group and 83 percent of the MTX group met the ACR 20 percent response criteria, and 41 percent and 58 percent, respectively, met the ACR 50 percent response criteria. The ACR 20 and the ACR 50 response rates in the CCII group were lower than those in the MTX group, and this difference was statistically significant.
The difference in adverse advents between the 2 groups was also statistically significant, but in favor of the CCII group. At 12 weeks, the CCII group reported 16 adverse events (13.55 percent of patients), while the MTX group reported 40 adverse events (38 percent of patients.
At 24 weeks, there 25 adverse events in the CII group (21 percent) and 50 adverse events in the MTX group (42 percent). Gastrointestinal symptoms were the most common adverse event. Other adverse events included insomnia, dizziness, headache, vomiting, and mouth ulcers. In general, side effects experienced in the CCII group were milder than those suffered by the MTX patients.
In the MTX group, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and white blood cell count decreased. There were no significant changes in these or other laboratory variables in the CCII group.
"Long-term observations in large numbers of RA patients are needed to confirm the efficacy of CCII," stresses the study’s lead author, Wei Wei, M.D. "If the efficacy were to be established, oral collagen would be a preferable treatment due to its minor toxicity."
Article: "A Randomized, Double-Blind, Multicenter, Controlled Clinical Trial of Chicken Type II Collagen in Patients With Rheumatoid Arthritis," Ling-Ling Zhang, Wei Wei, Feng Xiao, Han-Hua Xu, Chun-De Bao, Ling-Qing Ni, and Xing-Fu Li, Arthritis & Rheumatism (Arthritis Care & Research), July 15, 2008; 59:7, pp. 905-910.
SOURCE: American College of Rheumatology |
