The Latest News in Rheumatology
6/11/2002
Definition of Disease Flare in Ankylosing Spondylitis:
The Patients' Perspective
The Natural History of Ankylosing Spondylitis as
Defined by Radiological Progression
One-Year Open-Label Trial of Thalidomide in Ankylosing
Spondylitis
Medication Toxicity Among Patients With Ankylosing
Spondylitis
Recommendations About the Prevention and Management
of Tuberculosis in Patients Taking Infliximab (Remicade®)
According to a study published in the May 2002 Journal of Rheumatology,
researchers Sinead Brophy and Andrei Calin examined AS patients' perception
of the factors important in defining a flare since the medical community has very little understanding of what is a flare, why they occur, and what lasting
effects they have on the patient.
The disease course in AS typically appears to be characterized by bouts of
partial remission and flares, along with individual variations in terms of
prognosis and outcome. For AS patients, many of the factors defining a flare may
be subjective and difficult to quantify through physical examination.
Results: Two-hundred fourteen patients of the the Royal National Hospital
for Rheumatic Diseases were divided into smaller
groups. They discussed their experiences with flares, and each group had
to come to a single consensus definition of flare. They concluded the following:
- 100% of the groups said pain is the single worst aspect of a flare, and
that this acute pain differs from the normal pain they feel from
AS
- The majority also experience immobility, overwhelming fatigue, and
emotional symptoms, such as depression, anger, or fear
- There are two forms of flare:
1) Localized in one area-- This has been experienced by all participants.
Along with a stabbing pain, may be accompanied by fatigue, hot or burning
joints, cramp-like pain in the muscles, and emotional symptoms.
2)Generalized pain involving entire body-- Experienced by roughly 40% of the
patients questioned. Described as paralyzing pain, flu-like symptoms,
chronic fatigue, and extreme depression.
- Main perceived triggers of flare were stress (80%) and "overdoing
it" (50%).
The study concludes that AS flares are a devastating and depressing phenomenon in which
patients may seriously begin to doubt their own ability to cope with AS. While
the flare's unpredictability causes emotional symptoms, the researchers found
little long-term lasting damage to the joints caused by this phenomenon.
This was a summary of the study-- look for follow-up analysis in the
upcoming Spondylitis Plus issue.
In the June 2002 Journal of Rheumatology, researcher Sinead Brophy
and colleagues investigated
the disease development of AS by using patients' existing radiographs to judge
radiological change, which is a very important component in the assessment of AS
in patients.
Results: Researchers examined radiographs of 571 AS patients attending the Royal National Hospital
for Rheumatic Diseases. They concluded that AS is a progressive disease with
approximately 35% change every 10 years. Spinal involvement is an expression of
disease duration while the hips become involved in 25% of individuals, which may
help predict a more severe outcome for the cervical spine.
While the time interval between disease trigger and radiological change
remains unknown, the study found that backward extrapolation shows that the
disease process may start as young as 8 years of age.
According to the American College of Rheumatology Journal, Arthritis Care
& Research (June 2002), researchers David Yu and colleagues from the
University of California Los Angeles and the Chinese PLA General Hospital in
China coordinated a study to find whether Thalidomide is potentially useful in
treating patients with AS who have not responded to traditional treatment.
Thalidomide was the medication that caused an uproar in Europe in the 1960's
when it was given to pregnant women as a sedative, and produced major
deformities in their unborn children. As it turns out, Thalidomide is in a
similar class of medication to infliximab (RemicadeÒ)
and etanercept (EnbrelÒ), which are Tumor Necrosis
Factor - alpha blockers.
Results: Thirty male patients with AS were recruited into the 12 month
open study. Each patient took 200 mg of Thalidomide per day. While 80% showed at
least a 20% improvement, nine patients became completely pain-free. From the
results of this study, the researchers concluded that Thalidomide is a
reasonably promising drug in treatment-resisting AS patients.
Michael M. Ward and Susana Kuzis published findings in the American
College of Rheumatology Journal, Arthritis Care and Research (June
2002) from their study on the role of medication side effects and its potential
role in causing patients to stop taking their medication. The side effects of
several different medications were also compared with each other.
Results: 241 patients with AS took part in the longitudinal study, in
which researchers examined the duration of treatment and discontinuations due to
side effects of new courses of the following drugs: sulfasalazine, methotrexate,
ibuprofen, naproxen, indomethacin, diclofenac, piroxicam, nabumetone, and
celecoxib.
Side effects were reported in 6.7% (ibuprofen) to 47.3% (methotrexate) of the
new treatment courses. Between 2% (ibuprofen) and 23.5% (piroxicam) of courses
were discontinued due to these side effects. The duration of treatment was most
often limited by factors other than toxicity for each treatment. The time to discontinuation
for any reason and the time to discontinuation due to side effects did not
differ between sulfasalazine and methotrexate. According to the report, the same
held true for the non-steroidal anti-inflammatory medications (NSAIDs) involved
in the study, except for piroxicam, where discontinuation of treatment occurred
earlier than for other NSAIDs due to side effects.
From the results of this study, the researchers concluded that medication
side effects (toxicity) among patients with AS is common, but toxicity is an
uncommon cause of discontinuation of antirheumatic treatment.
According to a Joint Bone Spine 2002 article by D. Salmon on behalf of
the GTI and AFSSAPS (the French agency for healthcare product safety), an
unusually large number of tuberculosis cases has been reported in patients
taking infliximab. They issue the following recommendations for patients, and
for physicians in helping detect and manage tuberculosis in patients before and
after infliximab therapy.
In patients with latent tuberculosis (infection) or at high risk of
tuberculous reactivation:
- Tuberculosis reactivation is defined as a history of tuberculosis treated
before 1970 or not treated for at least 6 months, including at least 2
months on the rifampin-pyrizinamide combination; residual tuberculosis
lesions with no certainty that eradicative treatment was received;
intradermal tuberculin test done more than 10 years after last BCG
vaccination
- Patients with latent tuberculosis should undergo a detailed interview of
past history by physician and possible medical tests if deemed appropriate.
- Avoid contact with active tuberculosis-infected people.
In patients with active tuberculosis:
- If active tuberculosis is suspected or diagnosed, infliximab therapy must
be postponed.
- Patients suspecting active tuberculosis should undergo tests and receive
full course of antituberculous treatment.
Management of active tuberculosis diagnosed before or during infliximab
therapy:
- All patients must be informed to seek medical advice if they experience
signs or symptoms suggestive of tuberculosis (persistent cough, asthenia,
weight loss, or fever) during or within 6 months after discontinuation of
infliximab therapy.
- Patients with suspected tuberculosis should undergo immediate tests and
treatment.
Can infliximab therapy be resumed after tuberculosis therapy?
- Based on a lack of prospective data, they do not recommend resuming the
infliximab therapy.
- Yet if the infliximab therapy's value is considered major,
tuberculosis-free patients should wait at least 2 months after ending the
tuberculosis therapy before restarting infliximab.
- Current knowledge suggests isoniazid alone or with rafampin should be
given as long-term treatment for patients who resume infliximab use.
- Maintain careful monitoring by a medical team.
Conclusion: The researchers recommend following these suggestions to
reduce the frequency and severity of tuberculosis occurring during infliximab
therapy. Yet these recommendations will likely change in the near future because
many issues regarding this topic remain unsettled.