Although the pathogenetic mechanisms underlying the disease are unknown, rheumatoid arthritis is associated with human lymphocyte antigen (HLA)-DR4 and considered to be an autoimmune [self-attacking-self] disorder in which activated T cells participate.

Current treatments are inadequate in that they only partially control established rheumatoid arthritis. They also have side effects that limit use early in the disease process and interfere with prolonged administration.

Experimental findings [from two animal studies] provided the rationale for a pilot [Phase One trial], open-label dose-escalation and safety study in 10 [human] patients with recalcitrant rheumatoid arthritis. Subjects were taken off their immunosuppressive and disease-modifying drugs consisting of methotrexate, 6-mercaptopurine, azathioprine, or auranofin and fed 0.1 mg of solubilized type II collagen daily for 1 month and then switched to 0.5 mg for the next 2 months ...

Six of the 10 patients experienced a substantial clinical response, defined by a greater than 50% improvement in both swollen and tender joint counts with two additional disease measures improving by greater than 50% in morning stiffness, 15-m walk time, grip strength. These improvements lasted for at least 2 months after the treatment period. Complete disease remission lasting for 26 months occurred in one of the ten subjects; included discontinuation of nonsteroidal anti-inflamatory drugs (NSAID).

Based on the results of this Phase One study, a double-blind, placebo-controlled, Phase Two trial with 60 patients was undertaken to determine whether clinical efficacy could be demonstrated.

Among the collagen patients, the decline in the number of swollen joints, tender joints, and joint-swelling and tenderness indices were all significant in comparison to the placebo patients.

Four of the collagen patients (14%), as compared with none in the placebo group, had complete resolution of disease. At the beginning of the study these patients had had severe, active rheumatoid arthritis.

While collagen patients were off immunosuppressive drugs, stability or improvement occurred, whereas patients in the placebo group tended to deteriorate.

This controlled trial provides evidence that oral administration of type II collagen is both safe and can improve the daily physical challenges of rheumatoid arthritis.

Oral type II collagen is a preferable treatment because it appears to improve the health of the arthritic joint as evidenced by the joint functionality for several months after intake was cancelled.