Rheumatoid Arthritis of the Knee: Current Medical Management

Chapter 71 Rheumatoid Arthritis of the Knee

Current Medical Management

There has been substantial transformation, not without controversy, in the suggested algorithms for the treatment of rheumatoid arthritis (RA) over the past decade.^4,^6,²³ This has been accelerated by increasing understanding of the immune pathways of the disease itself (Fig. 71-1). Most of the nonsteroidal anti-inflammatory drugs (NSAIDs) have more limited use than in the past because of their cardiovascular risks through cyclooxygenase-2 (COX-2) inhibition¹⁵ or their risk for gastrointestinal intolerance¹⁶ and, in fact, have never appreciably affected the disease process. Corticosteroids reduce symptoms and systemic manifestations of RA, but chronic use is associated with frequent side effects and also does not appreciably prevent disease progression.¹⁷ Methotrexate and other disease-modifying antirheumatic drugs (DMARDs; Fig. 71-2) usually yield no immediate relief, but over time can control symptoms and are thought to delay progression of the disease. These remain the most often used agents by rheumatologists throughout the world for the treatment of RA.¹

Figure 71-1 Synovial T cells may be activated by a T-cell receptor (TCR) and costimulation pathways and by cytokine- or Toll-like receptor (TLR)–driven stimuli. In particular, the synovial milieu contains interleukin-12 (IL-12), IL-23, IL-6, and transforming growth factor beta (TGFβ) and, as such, promotes the differentiation of T-helper 1 (TH1) and TH17 cells. Regulatory T cells, although present, may not exhibit optimal regulatory activity. In rodent models, regulatory T cells are present in high numbers in the joints, whereas in human disease the relative contribution of these subsets remains unknown. Activated T cells mediate effector function in rheumatoid arthritis through the release of cytokines to promote downstream leukocyte and mesenchymal cell activation, through the provision of help to B cells and, in the case of CD8⁺ effector T cells, cytotoxic activity. They also activate macrophages, fibroblasts, and endothelial cells through direct cell contact. CD40L, CD40 ligand; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFNγ, interferon-γ; RANKL, receptor activator of nuclear factor-κB (RANK) ligand; TNF, tumor-necrosis factor.

(From McInnes IB, Schett G: Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 2007;7:429–442.)

Figure 71-2 Recommendations of indications for the use of nonbiologic DMARDs in RA patients who have never received DMARDs. These recommendations do not specifically include the potential role of glucocorticoids or NSAIDs in the management of patients with RA. Therapies are listed alphabetically. A, Disease duration <6 months. B, Disease duration of 6 to 24 months. C, Disease duration >24 months. ‡, Includes functional limitation (defined using standard measurement scales such as Health Assessment Questionnaire score or variations of this scale), extra-articular disease (e.g., presence of rheumatoid nodules, secondary Sjögren’s syndrome, RA vasculitis, Felty’s syndrome, and RA lung disease), rheumatoid factor positivity, positive anticyclic citrullinated peptide antibodies, or bony erosions by radiography, §, only recommended for patients with high disease activity with features of poor prognosis; ||, only recommended for patients with moderate disease activity irrespective of prognostic features and patients with high disease activity without features of poor prognosis; #, only recommended for patients with high disease activity without features of poor prognosis; HCQ, hydroxychloroquine; LEF, leflunomide; MTX, methotrexate; MIN, minocycline; SSZ, sulfasalazine.

(From Saag K, Teng G, Patkar N, et al: American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008;59:762–784.)

Nevertheless, recent advances by the novel biologic agents (biologics; Fig. 71-3), such as the tumor necrosis factor-alpha (TNF-α) inhibitors and anti-CD20 monoclonal antibodies, have allowed many patients with RA to experience improvement in symptoms, function, and quality of life to a degree they might not have achieved in the past. Etanercept, infliximab, adalimumab, anakinra, golimumab, certolizumab pegol, rituximab, abatacept and most recently, tocilizumab are currently U.S. Food and Drug Administration (FDA) approved for the treatment of rheumatoid arthritis. Thus, therapeutic decision making for this disease has become more complex for clinicians, with many conflicting factors playing increasingly important roles. According to the most objective measures of RA progression, very early intervention with conventional DMARDs is cost-effective whereas that of very early intervention with biologics remains unclear.¹³ However, more recent data indicate that biologic therapy is associated with increases in workforce participation in patients typically expected to experience progressively deteriorating ability, which could result in significant indirect cost benefits to society.³