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Novel Therapeutics for Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis
By Prachaya Nitichaikulvatana, M.D., (Dr. Oak), Division of Rheumatology
The past decade has witnessed the development of a number of novel therapeutic agents that provide new treatment options and hope for arthritis sufferers. These therapeutic agents have, for many patients, put arthritis into remission, leading to very low levels of disease activity, improved functional capability, and a higher quality of life.
Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) are the most common forms of inflammatory arthritis. RA is a progressive systemic inflammatory disease characterized by chronic synovial inflammation that may result in damage to cartilage and bone, leading to a decline in function and joint deformities. The prevalence of RA has been estimated to range between 0.55% and 1.0%, and it is estimated that nearly 1.3 million Americans 18 years or older have RA.
Psoriatic Arthritis (PsA) occurs in up to 30% of individuals with psoriasis and is characterized by both chronic synovial and enthesial inflammation. The prevalence of PsA has been estimated to range between 0.3% and 1.0%. Ankylosing Spondylitis (AS) is an inflammatory process in the axial skeleton that may ultimately result in spinal fusion. Among studies of white Europeans and East Asians, the reported prevalence of AS has ranged between 0.3% and 0.9%.
Treatment Strategies for Rheumatoid Arthritis Patients
The current treatment of rheumatoid arthritis employs the strategy of early and aggressive medical therapy. Once the diagnosis has been established, low-dose weekly methotrexate (MTX) therapy typically is initiated to attempt to achieve a “low-disease activity” (LDA) state. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be employed for symptomatic relief. Other disease-modifying anti-rheumatic drugs (DMARDs), such as hydroxychloroquine, sulfasalazine, and leflunomide, may also be employed in some patients, either alone or in combination with MTX.
If an LDA state cannot be achieved with MTX, either alone or in combination with DMARDs, a biologic agent usually is added to background MTX therapy. Biologic agents with several different mechanisms of action have now been approved by the United States Food and Drug Administration (FDA). There are now five TNF inhibitors that are FDA approved for the treatment of RA, including Etanercept (Enbrel®), Infliximab (Remicade®), Adalimumab (Humira®), Golimumab (Simponi®), and Certolizumab pegol (Cimzia®).
In patients with moderate to severe RA, Anakinra (recombinant human interleukin-1 receptor antagonist) has been shown to have beneficial outcomes in combination with MTX in clinical trials. A selective inhibitor of T-cell co-stimulation, Abatacept is another option for treatment of resistant RA. Tocilizumab, a humanized antibody against IL-6 receptor, was recently approved by the FDA for use in RA and is administered by intravenous infusion. B-lymphocyte depletion using a monoclonal antibody to CD 20 (Rituximab) plus MTX has been effective in randomized trials of patients with RA who were resistant to MTX alone as well as those resistant to TNF inhibitor.
Rheumatologists have witnessed significant progress in the development of treatment options for RA over the past 10 years. The debilitating complications and deformities once synonymous with RA are now mostly kept at bay with the use of biologic agents. When used in combination with standard DMARDs like MTX, not only do biological agents significantly minimize joint damage, but also greatly improve function and quality of life. Patients now have options for being pain-free or reducing the pain, stiffness, and fatigue due to RA. Many are now able to resume their daily lives and recreational activities.
Treatment Options for Psoriatic Arthritis and Ankylosing Spondylitis
The treatment of psoriatic arthritis parallels that of RA and uses many of the same therapeutic agents in conjunction with conventional DMARDs. The current FDA-approved TNF inhibitors treatments are Etanercept, Infliximab, Adalimumab, and Golimumab. Certolizumab pegol hasnot yet been approved for treatment of PsA and Phase III trials are underway.
In patients with AS, the first line treatment of choice is NSAIDs, followed by TNF inhibitors, Namelt Etanercept, Infliximab, Adalimumab, and Golimumab, which have been approved for AS, as well as for PsA. Using MR imaging, TNF inhibitors have also been shown to reduce vertebral body osteitis in patients with AS and are believed to slow structural progression of AS.
Side Effects
The adverse effects associated with novel biologic agents like TNF inhibitors, interleukin (IL)-1 receptor antagonists, selective inhibitors of T-cell co-stimulation, B-cell monoclonal antibodies, and IL-6 receptor monoclonal antibodies are potentially serious. However these risks must be weighed against potential benefits and adverse effects, and should be managed by rheumatologists.
These medications should be stopped if patients develop any infections, as biologics cause immunosuppression. There have been reports of serious infections caused by bacteria, fungi, or viruses resulting in systemic spread, including tuberculosis (TB) and histoplasmosis. Any patient being considered for biologic treatment, especially TNF inhibitors and Tocilizumab, must have PPD skin testing prior to initiation of the treatment. Patients with evidence of latent TB infection should be treated with prophylactic antituberculous therapy before starting TNF inhibitors. TNF inhibitors and Tocilizumab should be avoided in patients with pre-existing or recent onset of CNS demyelinating disorders such as multiple sclerosis. These medications should be managed by rheumatologists, in coordination with primary care physicians.
Conclusion
Recent years have witnessed a dramatic growth in treatment options for patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The current strategy focuses on early and aggressive medical therapy, generally with low-dose weekly methotrexate (MTX), to achieve a “low-disease activity” state, coupled with NSAIDs and disease-modifying anti-rheumatic drugs. If an LDA state cannot be achieved in this manner, the clinician has a number of FDA-approved biologic agents available to use in conjunction with MTX therapy.
The New England Neurological Associates Division of Rheumatology offers a full range of medical services in the diagnosis and treatment of arthritis and other diseases of the joints, bones and muscles including:
- Arthritis associated with inflammatory bowel diseases
- Bursitis/tendonitis
- Diseases which cause inflammation of the spine (ankylosing spondylitis and related conditions)
- Diseases which cause inflammation of blood vessels (vasculitis) including but not limited to giant cell(temporal) arteritis, Wegener’s granulomatosis, hypersensitivity vasculitis, and cryoglobulinemia
- Gout, pseudogout, and other crystal-induced arthritis
- Inflammatory diseases with muscular involvement polymyalgia rheumatica, polymyositis/dermatomyositis)
- Musculoskeletal pain syndromes
- Osteoarthritis (also known as degenerative arthritis or “wear-and-tear” arthritis)
- Osteoporosis and other bone diseases
- Psoriatic arthritis
- Rheumatoid arthritis
- Sjogren’s syndrome
- Scleroderma (local and systemic sclerosis)
- Systemic lupus erythematosus and other forms of lupus
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