Susceptibility to rheumatoid arthritis (RA) is complex; although a number of genetic susceptibility loci have been identified that appear to confer increased risk. Among these, genes encoding sequence variants in the major histocompatibility complex (MHC) class II molecule, known as the “shared epitope” (SE), have been known for decades and have the strongest link to RA susceptibility.
Atacicept is a recombinant fusion protein that binds and neutralizes two molecules important for the maturation, proliferation, and survival of B cells: BLyS and APRIL. While B-cell depleting therapies have demonstrated efficacy in RA, atacicept differs from the anti-CD20 targeted monoclonal antibodies, such as rituximab, as its effects extend over the entire lineage of B lymphocytes, including plasma cells.
RA is associated with an increase in cardiovascular (CV) events, such as myocardial infarction (MI) and sudden cardiac death. Inflammatory cytokines, such as TNF-α, are implicated in atherothrombosis and the RA disease state, potentially explaining the increased risk of CV events in RA. The use of TNF inhibitors was associated with a reduced risk of cardiovascular events in RA patients in one study, although it is not clear whether these effects are due to unique features of TNF inhibitors or are a consequence of non-specific suppression of inflammation.
The potential for hepatotoxicity is a well-recognized feature of therapy with a number of DMARDs in rheumatoid arthritis (RA), with methotrexate (MTX) being the most common utilized. Concomitant use of other hepatotoxic agents has the potential to compound the risk of significant liver damage. Among these, isoniazid (INH) is increasingly used in RA patients receiving MTX with evidence of latent tuberculosis infection (LTBI) or prior active tuberculosis for whom TNF inhibitor therapy is planned.
Patients with early inflammatory arthritis not meeting classification criteria for rheumatoid arthritis (RA) may have treatment delayed until typical phenotypic features accumulate. Due to the concern for toxicities of DMARDs, patients are often treated with NSAIDs and simple analgesics during this period. However, delay in DMARD treatment in early RA has been shown to result in poorer outcomes, such as irreversible radiographic damage.
In addition to its role in calcium hemostasis and bone metabolism, vitamin D also appears to be an important regulator of immune function. However, its role in modulating RA disease activity has not been studied.
Older person with rheumatoid arthritis (RA) make up an increasing proportion of those treated with biologic disease modifying anti-rheumatic agents (DMARDs). The safety of these agents may differ for this subgroup of older RA patients, yet effects have generally not been selectively studied in this population.
A strong association between chondrocalcinosis, resulting from calcium pyrophosphate dihydrate (CPPD) deposition, and knee osteoarthritis (OA) is firmly established. However, despite the association, a causative pathogenic role for CPPD crystals on the progression of articular degeneration in the knee has not been definitively demonstrated.
Although compelling, no clear-cut links between dietary factors and the risk of developing rheumatoid arthritis (RA) have been confirmed. Recent investigations have implicated increased consumption of red meat as a risk factor for incident inflammatory arthritis.
The molecular mechanisms leading to erosive joint damage in some, but not all, patients with rheumatoid arthritis (RA) are incompletely understood. Downstream effects of inflammatory cytokines produced by rheumatoid synovium include the induction of RANKL, a powerful osteoclast activator, the action of which is physiologically opposed by its naturally occurring antagonist osteoprotegerin (OPG).