Kunxian Capsule for Rheumatoid Arthritis: Inhibition of Inflammatory Network and Reducing Adverse Reactions Through Drug Matching

Chapter summary The prevalence of rheumatoid arthritis (RA) is relatively constant in many populations, at 0.5–1.0%. However, a high prevalence of RA has been reported in the Pima Indians (5.3%) and in the Chippewa Indians (6.8%). In contrast, low occurrences have been reported in populations from China and Japan. These data support a genetic role in disease risk. Studies have so far shown that the familial recurrence risk in RA is small compared with other autoimmune diseases. The main genetic risk factor of RA is the HLA DRB1 alleles, and this has consistently been shown in many populations throughout the world. The strongest susceptibility factor so far has been the HLA DRB1*0404 allele. Tumour necrosis factor alleles have also been linked with RA. However, it is estimated that these genes can explain only 50% of the genetic effect. A number of other non-MHC genes have thus been investigated and linked with RA (e.g. corticotrophin releasing hormone, oestrogen synthase, IFN-γ and other cytokines). Environmental factors have also been studied in relation to RA. Female sex hormones may play a protective role in RA; for example, the use of the oral contraceptive pill and pregnancy are both associated with a decreased risk. However, the postpartum period has been highlighted as a risk period for the development of RA. Furthermore, breastfeeding after a first pregnancy poses the greatest risk. Exposure to infection may act as a trigger for RA, and a number of agents have been implicated (e.g. Epstein–Barr virus, parvovirus and some bacteria such as Proteus and Mycoplasma). However, the epidemiological data so far are inconclusive. There has recently been renewed interest in the link between cigarette smoking and RA, and the data presented so far are consistent with and suggestive of an increased risk.

Interleukin-17A (IL-17A) is elaborated by the T helper 17 (T(H)17) subset of T(H) cells and exhibits potent proinflammatory properties in animal models of autoimmunity, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveitis. To determine whether IL-17A mediates human inflammatory diseases, we investigated the efficacy and safety of AIN457, a human antibody to IL-17A, in patients with psoriasis, rheumatoid arthritis, and chronic noninfectious uveitis. Patients with chronic plaque-type psoriasis (n = 36), rheumatoid arthritis (n = 52), or chronic noninfectious uveitis (n = 16) were enrolled in clinical trials to evaluate the effects of neutralizing IL-17A by AIN457 at doses of 3 to 10 mg/kg, given intravenously. We evaluated efficacy by measuring the psoriasis area and severity index (PASI), the American College of Rheumatology 20% response (ACR20) for rheumatoid arthritis, or the number of responders for uveitis, as defined by either vision improvement or reduction in ocular inflammation or corticosteroid dose. AIN457 treatment induced clinically relevant responses of variable magnitude in patients suffering from each of these diverse immune-mediated diseases. Variable response rates may be due to heterogeneity in small patient populations, differential pathogenic roles of IL-17A in these diseases, and the different involvement or activation of IL-17A-producing cells. The rates of adverse events, including infections, were similar in the AIN457 and placebo groups. These results support a role for IL-17A in the pathophysiology of diverse inflammatory diseases including psoriasis, rheumatoid arthritis, and noninfectious uveitis.

To conduct a systematic review of incidence and prevalence studies of rheumatoid arthritis (RA), based on the 1987 revised American College of Rheumatology (ACR) criteria, to compare their methodologies and summarize their results, and to investigate the possible geographic variations and changes over time in the frequency of the disease. We conducted a Medline search between January 1988 and December 2005. Studies reporting the incidence and prevalence of RA in adult populations (16 to 20 years and over), based on 1987 ACR criteria, were eligible for inclusion. From each study included, we extracted the country, year of publication, type of study (retrospective, prospective, or cross-sectional), and incidence or prevalence rates. The study areas were grouped into (a) North American countries; (b) north European countries; (c) south European countries; and (d) developing countries. We examined the geographical differences of prevalence and incidence rates using the Mann-Whitney and the Kruskall-Wallis tests. A total of 28 studies were identified meeting the inclusion criteria. Nine were incidence studies, 17 were prevalence studies, and 2 estimated both prevalence and incidence rates. Incidence studies were not available from developing countries. There is a significant difference of prevalence estimates between northern European and American countries and developing countries. South European countries have lower median incidence rates than North American and north European countries. As concerning the time trends of RA occurrence, only 3 incidence studies provided secular data from the same study area, based on ACR criteria, using the same methods of case ascertainment. Two of these studies indicate a decreasing incidence of RA in Finland and United States of America. The occurrence of RA varies among countries and areas of the world. A decreasing trend has been observed in countries characterized by high rates of RA incidence and prevalence. However, the relatively small number of studies for most areas of the world and the lack of incidence studies for the developing countries limits the understanding of worldwide RA epidemiology.