JointHealth™ insight   December 2008

In this on-line issue of JointHealth monthly, we present information on treatment guidelines for rheumatoid arthritis and psoriatic arthritis. These guidelines have been developed by scientific experts and, in some cases, patients living with arthritis. Treatment guidelines are developed to assist doctors in treatment planning for people living with disease. Also included in this issue is a spotlight on fibromyalgia.
Guidelines for the treatment of rheumatoid arthritis and psoriatic arthritis

Treatment guidelines are important tools for doctors and health care providers. They help doctors to make timely, evidence-based treatment decisions along with their patients living with arthritis. In addition, they are useful in ensuring that care and treatment is standardized and that government and private insurers' resources are being used in the best interests of the person living with the disease and as cost-efficiently as possible.

How are treatment guidelines created?
While there are different methods for establishing treatment guidelines, and different organizations have produced guidelines for various diseases, in general, the process follows a very similar pattern.
  1. A panel is established, made up of physicians, health care professionals (such as nurses or physiotherapists), health economists, and patients/consumers.
  2. Following this, the panel reviews all the relevant quantitative and qualitative literature about the topic at hand, looking at the benefits, harms, cost effectiveness and public policy issues and develops draft guidelines.
  3. The draft guidelines are then reviewed by experts in the field to get a sense of the clinical experiences of these diseases and treatments so as to get consensus on the draft guidelines.
  4. Once consensus is achieved, the guidelines are published.
Recommendations for the Use of Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis1
The American College of Rheumatology is an "organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy, and practice support that foster excellence in the care of people with arthritis and rheumatic and musculoskeletal diseases". In recent years, they have developed practice guidelines for the treatment of various forms of arthritis, including rheumatoid arthritis, osteoarthritis, lupus and pediatric forms of arthritis.

In establishing recommendations for the treatment of rheumatoid arthritis, the panel created separate ones for early rheumatoid arthritis (less than 6 months) and for those patients who have had rheumatoid arthritis for longer than 6 months. The panel also separated the anti-TNF medications including: [etanercept (Enbrel®), infliximab (Remicade®) and adalimumab (Humira®)], from the two new biologic response modifiers, rituximab (Rituxan®) and abatacept (Orencia®).

It is important to note that in creating recommendations about the use of anti-TNF medications, the panel made no distinctions between the three types of anti-TNF medications available on the market. This means that all of these three medications were considered interchangeable.

Anti-TNF medications in patients with early RA (defined as less than 6 months):
Anti-TNF medications were not recommended for patients with RA for less than 6 months who had:
  • low or moderate disease activity
Anti-TNF medications were recommended, with methotrexate, for patients with disease less than six months who:
  • have high disease activity for more than 3 months;
  • never received disease-modifying antirheumatic drugs (DMARDs)
  • a poor prognosis* and;
  • ability to afford treatment or insurance to cover the costs
* poor prognosis (or prediction) in these guidelines means: active disease, with high, tender and swollen joint counts, evidence of damage through x-rays, high level of rheumatoid factor (RF), high erythrocyte sedimentation rate (ESR). In addition, important predictors of potentially bad disease include: older age, female sex, cigarette smoking and early disability.

Anti-TNF medications in patients with RA for 6 months or greater:
For patients who have had RA for 6 months or more, the ACR recommended the use of anti-TNF agents (interchangeably) for patients with:
  • an inadequate response to treatment with methotrexate only,
  • moderate disease activity and poor prognosis*
  • high disease activity, regardless of prognosis*
an inadequate response to methotrexate therapy used in combination with residual disease activity(persistent swollen joints, persistent morning stiffness and persistent inflammation based on blood tests)

  • regardless of prognostic features or;
  • an inadequate response to a series of other nonbiologic DMARDS with residual disease activity, regardless of prognostic features
Along with anti-TNF medications, recommendations were also created for the use of newer biologics, including abatacept (Orencia®) and rituximab (Rituxan®).

The use of abatacept (Orencia®) for RA was recommended for those patients with:
  • an inadequate response to methotrexate in combination with DMARDS, at least moderate disease activity and features of a poor prognosis or;
  • an inadequate response to a series of other non-biologic DMARDS, at least moderate disease activity and features of a poor prognosis.
The use of rituximab (Rituxan®) was recommended for RA patients with:
  • an inadequate response to methotrexate in combination with DMARDS, at least moderate disease activity and features of a poor prognosis or;
  • an inadequate response to a series of other non-biologic DMARDS, at least moderate disease activity and features of a poor prognosis.
It is not recommended to use more than one biologic medication at a time because this has been shown to result in additional side effects.

1Saag et al. (2008). Arthritis & Rheumatism (Arthritis Care & Research), Vol. 59, No. 6, June 15, pp 762-784

Guidelines for the Management of Psoriatic Arthritis2

As with rheumatoid arthritis, treatment guidelines have recently been established for psoriatic arthritis. These were developed by GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), which is an international group made up of rheumatologists, dermatologists, and patient advocates. In October of 2008, they issued comprehensive treatment guidelines for each of the main manifestations of psoriatic arthritis (PsA): peripheral arthritis (feet and hands), skin and nail psoriasis, axial disease (spine), dactylitis (swelling of the fingers) and enthesitis (inflammation at the point where tendons enter the bone).

To create these guidelines, members of GRAPPA went through similar steps to the ACR. First, they conducted literature reviews of the relevant research on treatment for the most significant forms of PsA. After this, they developed draft treatment recommendations for each of the 5 manifestations, which were then reviewed by all members of GRAPPA to get a consensus opinion. Finally, in addition to the recommendations, and to better help doctors make treatment decisions for individual patients, this group also created an evidence-based "grid" to take into consideration the severity of each of the five manifestations of psoriatic arthritis to help physicians make individual patient decisions that are evidence based.

Specific treatment recommendations for PsA include the following:

For peripheral (feet and hands) arthritis, treatment options include:
  • nonsteroidal anti-inflammatory drugs (NSAIDs)
  • intra-articular glucocorticoid injections (steroid injections)
  • DMARDs
    • sulfasalazine, leflunomide, methotrexate, cyclosporine
  • tumor necrosis factor inhibitors (anti-TNF)
    • etanercept (Enbrel®), infliximab (Remicade®) and adalimumab (Humira®)
    • for patients who fail at least one DMARD
    • for patients with poor prognosis*
* This means number of inflamed joints, high ESR, failure of other medications, damage seen through x-rays or by physician, loss of function (HAQ), diminished quality of life (SF-36).

For the treatment of skin and nail psoriasis:
Skin disease:
  • Phototherapy: UVB/NbUVB, oral PUVA, bath PUVA (light-sensitizing medications)
    • cyclosporin
  • Anti TNF
    • etanercept (Enbrel®) and infliximab (Remicade®)
Nail disease
  • Retinoids (vitamin A drugs)
  • Oral PUVA (light-sensitizing medication)
  • Cyclosporine
  • Anti-TNF
    • etanercept (Enbrel®) and infliximab (Remicade®)
For the treatment of Axial (spine) disease:
  • NSAIDs
  • Physiotherapy
  • Analgesia (pain killer)
  • Steroid injection of sacroiliac joint
  • Anti-TNF
    • etanercept (Enbrel®), infliximab (Remicade®) and adalimumab (Humira®)
For the treatment of Enthesitis:
  • NSAIDs
  • Physical therapy
  • Corticosteroids
  • DMARDs
  • Anti-TNF
    • infliximab (Remicade®) and etanercept (Enbrel®)
For the treatment of Dactylitis:
  • NSAIDs
  • Corticosteroids
  • DMARDs
  • Anti-TNF
    • Infliximab (Remicade®)
Please remember that this material is provided for information purposes only. If you have any questions about your treatment, or these recommendations, you should speak to your rheumatologist or health care provider.

2Ritchlin, CT, et al. (2008). Ann Rheum Dis, published online, October 24, 2008

Fibromyalgia is a condition characterized primarily by chronic widespread pain (CWP) in the muscles, ligaments and tendons, and a heightened sensitivity to touch resulting in pain that can last for months.

There are also other common signs and symptoms of fibromyalgia, which can include3:
  • Depression
  • Mood changes
  • Numbness or tingling sensations in the hands and feet
  • Concentration problems
  • Pain in the chest
  • Dry eyes, skin and mouth
  • Painful menstrual periods
  • Dizziness
  • Anxiety
  • Overwhelming fatigue, even after a good night's sleep
The prevalence of fibromyalgia ranges from 0.5% to 5.8% and is more common in women than in men4.

The cause of fibromyalgia remains unknown, but several theories exist. One is called "central sensitization"5. The thinking behind this idea is that people with fibromyalgia have a lower threshold for pain due to an increased sensitivity to pain signals in the brain. It has been suggested that this may be related to the presence of higher than normal levels of a nerve chemical, called "substance P", in the spinal fluid of people with fibromyalgia. This chemical transmits and amplifies pain signals to and from the brain. In other words, for someone with fibromyalgia, this theory suggests that the "volume control" for pain is turned up too high in the brain6.

Other ideas about the cause of fibromyalgia include:
  • Dysfunction of the autonomic nervous system, which controls bodily functions that you don't consciously control
  • Chronic sleep disorders
  • Emotional stress or trauma
  • Immune or endocrine system dysfunction
The diagnosis of fibromyalgia is difficult because there is no specific diagnostic laboratory test. Therefore, a doctor makes a diagnosis of fibromyalgia based on the patient's history and physical examination. The American College of Rheumatology (ACR) has created guidelines to help with assessment and diagnosis of fibromyalgia, and to assist in the assessment and study of the condition. According to the ACR, to be diagnosed with fibromyalgia a person must:
  • have experienced widespread aching pain for at least three months, and
  • have a minimum of 11 locations on your body that are abnormally tender under relatively mild, firm pressure.
Treatment of fibromyalgia
While there is no known cure for fibromyalgia, treatments exist that can help to manage the symptoms of the disease. In general, treatment for fibromyalgia includes both medication (for symptom management) and self-care.

Lifestyle changes can have a strong positive impact on the relief of fibromyalgia symptoms and enable a person to better cope with their disease. These include:
  • Exercise - this is perhaps the single most effective "treatment"; exercise helps with managing the symptoms of the disease as well as contributes to emotional well being
  • Reducing stress-find ways to deal with or minimize the stress in your life
  • Getting enough sleep - because fatigue is such a central aspect of fibromyalgia, it is important to make sure that you get enough sleep.
  • Balanced life - pace yourself, try not to take too much on in your work or family life
  • Healthy lifestyle - eat healthy foods
When exercise and other lifestyle approaches are not enough, medications can be added to a person's treatment plan to help reduce the pain of fibromyalgia and improve sleep. Some common medication choices your doctor may prescribe include789:
  • Analgesics - such as acetaminophen (such as Tylenol®)
  • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen (or Advil®) and naproxen (or Naprosyn®),
  • Antidepressants - such as tricyclic anti-depressants (TCA), selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)
  • Muscle relaxants - to help treat pain and muscle spasms.
  • Antiepileptic medications - such as gabapentin (Neurontin®) and pregabalin (Lyrica®), which was the first drug approved by the Food and Drug Administration (FDA) to treat fibromyalgia
In addition to the medications listed above, prescription sleeping pills have been used to help deal with sleep disturbances; however, it is important to note that many doctors advise against their long-term use because the body can become resistant to them, which may result in more sleeping problems.

Benzodiazepines have also been used, but like with sleeping pills, doctors often avoid using these medications because they are addictive and can become habit forming.

Cognitive behavior therapy can also be useful as it helps a person with fibromyalgia to develop self-management skills for dealing with stressful situations.

3Mayo Clinic website
4Uceyler et al. (2008). "A systematic review on the effectiveness of treatment with antidepressants in Fibromyalgia Syndrome" in Arthritis and Rheumatism, vol. 59, 9:1279-1298.
5Mayo Clinic website
6American College of Rheumatology website
8Uceyler et al. (2008)
9Mayo Clinic website

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Over the past 12 months, ACE received unrestricted grants-in-aid from: Abbott Laboratories Ltd., Amgen Canada / Wyeth Pharmaceuticals, Bristol-Myers Squibb Canada, GlaxoSmithKline, Hoffman-La Roche Canada Ltd., Merck Frosst Canada, Pfizer Canada, Schering-Plough Canada, and UCB Pharma Canada Inc. ACE also receives unsolicited donations from its community members (people with arthritis) across Canada.

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