Osteoarthritis (OA) and rheumatoid arthritis (RA) are both characterized by structural degradation and gradual destruction of cartilage, especially in the synovial joints, causing progressive, persistent inflammation leading to pain, joint erosion and functional impairment.

OA has always been considered to be mechanical in origin, arising due to normal wear-and-tear of joint cartilage. RA on the other hand, is a systemic disease arising due to an autoimmune inflammatory reaction to joint cartilage and synovial tissue. The affected person’s own immune system attacks joint tissues, especially the protective cartilage for yet unknown reasons.

Synovial fibroblasts, which can be identified at the site of invasion of the rheumatoid synovium into the adjacent cartilage and bone, have been implicated in the pathophysiology of joint destruction in RA.1,2 As the disease progresses, the inflamed synovium invades and damages the cartilage and bone of the joint. Surrounding muscles, ligaments and tendons become weakened and a generalized bone loss may occur leading to destruction of the joint architecture. Current therapies for rheumatoid arthritis are often unsatisfactory because of inadequate efficacy and/or unacceptable toxic effects. RA patients have cellular sensitivity to collagen, implicating autoimmunity to type II collagen in the pathogenesis of the disease. Antigen-specific immunosuppression of autoimmunity to type II collagen may help alleviate RA. For this purpose, an orally active antigen solution Vital 3, containing type II collagen, has been developed and studied for safety and efficacy in reducing the signs and symptoms of RA.4

Desensitizing the immune system by orally administering an antigen characteristic of the inflamed tissue would result in a tissue-specific decrease in inflammatory response.

Oral tolerance is defined as the suppression of immune response to antigens that have been previously administered by the oral route. 

Acting as a mucosal vaccine in the lymphoid tissue surrounding the gut (Peyer’s Patches), Vital 3 type II collagen, at low doses, stimulates the production of regulatory T cells (Tregs) specific for peptides from type II collagen. These Tregs (Th2, Th3) circulate throughout the body and secrete anti-inflammatory cytokines (IL-4, IL-10 and TGFβ) when they encounter the same peptides properly displayed on the surface of antigen-presenting cells in synovial tissue. Because type II collagen antigens are found predominantly in synovial tissue, the immunosuppression is highly localized to joints.

Vital 3 type II collagen has been extensively studied under controlled, pre-clinical and clinical trial conditions. In vivo and in vitro studies have revealed no signs of local gastrointestinal tract or systemic toxicity.

Three multiple-dose toxicity studies were conducted in rats and clinical observations, clinical pathology measurements, absolute and relative organ weights, gross necropsy and histopathologic evaluations indicated that Vital 3 type II collagen is safe and nontoxic. Through Ames’ bacterial reverse mutation assay, it was demonstrated that Vital 3 type II collagen did not have any mutagenic effects.

Additionally, the dilute acetic acid solution used to formulate Vital 3 type II collagen has been shown to comply with the USP Antimicrobial Preservation Effectiveness Test requirements, ensuring that it is highly unlikely for any pathogenic bacteria or yeast to survive or propagate in the Vital 3 type II collagen solution.

An Integrated Safety Analysis of two open-label and five randomized, double-blind, placebo controlled human studies indicates that there are no differences in the safety parameters measured between subjects administered Vital 3 type II collagen and subjects administered a placebo. No clinically meaningful differences in adverse events, clinical laboratory values, antibody titers or vital signs are observed. Vital 3 type II collagen is exceptionally safe and well tolerated.