Efficacy of Etanercept for Treatment of Crohn's Related Spondyloarthritis But Not Colitis

A Polyarticular Onset Predicts Erosive and Deforming Disease in Psoriatic Arthritis

Interactions Between Herbal Medicines and Prescribed Drugs: A Systematic Review

Does Aspirin Negate the GI Advantages of Coxibs?

Does Acetaminophen Cause GI Toxicity at High Doses?

TNF-alpha inhibitors etanercept (Enbrel®) and infliximab (Remicade®) have shown to be effective in the treatment of the spondyloarthropathies (SpA) as a whole. Researchers H. Marzo-Ortega and colleagues from the University of Leeds and Leeds General Infirmary in the UK summarize the findings of their study on etanercept's effect on Crohn's disease and colitis associated with SpA. Results are published in a recent issue of the Annals of Rheumatic Diseases.

In treating two patients with SpA and associated Crohn's disease, etanercept showed an excellent response on the patients' arthritic symptoms, whereas their Crohn's disease persisted or flared.

Only infliximab was successful in the treatment of colitis in patients with Crohn's SpA.

This suggests that the effect of TNF-alpha in SpA differs between the joint and the bowel.

A common concern for people with spondylitis is whether or not they will develop a more severe form of the disease. With this in mind, researchers R. Queiro-Silva and colleagues from Spain (Hospital San Agustin and Hospital Monte Naranco) wanted to analyze the factors predicting "erosive-deforming" disease in patients with psoriatic arthritis. Their findings were published in the latest issue of the Annals of the Rheumatic Diseases.

Results: 71 patients (44 men and 27 women, average age 47 years) diagnosed as having psoriatic arthritis took part in the study. Each person was studied and followed up from the period of January 1991 to June 2001.

The researchers define "erosive and deforming disease" by the presence of erosions, narrowing of joint space, subluxation (partial joint dislocation), and/or hardening of small joints (such as the ankles, knees, shoulders).

They found the following:

• 32 of 71 (45%) patients had developed "erosive and deforming" disease.
• Of these 32, 18 (56%) had polyarticular onset (five or more swollen joints)
• Men had fewer erosions than women.
• HLA-B27 positive patients showed less erosive disease than HLA-B27 negative patients.
• Patients with "erosive and deforming" disease tended to have poorer functional performance

The researchers conclude only a polyarticular onset remained as an indicator of "erosive and deforming disease", and could be used to help predict whether a psoriatic arthritis patient may need more aggressive treatment at an earlier stage in the treatment process than is currently being used.

The use of herbal medicines is widespread, yet documented herb-drug interactions are sparse.

AA Izzo and E. Ernst from the Department of Experimental Pharmacology at the University of Naples, Italy, reviewed previous literature to determine possible interactions between the seven top-selling herbal medicines (ginkgo, St. John's wort, ginseng, garlic, echinacea, saw palmetto, and kava) and prescribed drugs.

They collected herb-drug interaction data from case reports, case series, clinical trials, and other types of investigations in humans. Findings were reported in the National Library of Medicine.

The researchers found the following:

• St. John's wort -- a.k.a Hypericum perforatum:
  Lowers blood concentrations of cyclosporin (GENGRAF), amitriptyline (ELAVIL or ENDEP), digoxin (DIGOXIN), indinavir (CRIXIVAN), phenprocoumon and theophylline (used in numerous medications); causes intermenstrual bleeding, delirium or mind serotonin syndrome when used concomitantly with oral contraceptives (ethinylestradiol/desogestrel), loperamide or selective serotonin-reuptake inhibitors (sertaline, paroxetine, nefazodone).
• Ginkgo -- a.k.a. Ginkgo biloba:
  Causes bleeding when combined with warfarin (COUMADIN), raised blood pressure when combined with a thiazide diuretic, and coma when combined with trazodone (TRAZODONE or DESYREL).
• Ginseng -- a.k.a. Panax ginseng:
  Lowers blood concentrations of alcohol and warfarin (COUMADIN), and induces mania if used concomitantly with phenelzine (NARDIL).
• Garlic -- a.k.a. Allium sativum:
  Changes pharmacokinetic variables of paracetamol (TYLENOL), decreases blood concentrations of warfarin (COUMADIN), and produces hypoglycaemia when taken with chlorpropamide (DIABINESE).
• Kava -- a.k.a. Piper methysticum:
  Increases "off" periods in Parkinson patients taking levodopa (LARODOPA and DOPAR) and can cause a semicomatose state when given concomitantly with alprazolam (XANAX).
• Echinacea -- a.k.a. echinacea angustifolia, E. purpurea, E. pallida:
  No interactions found.
• Saw palmetto -- a.k.a. Serenoa repens:
  No interactions found.

Izzo and Ernst conclude that interactions between herbal medicines and synthetic drugs exist and can have serious medical consequences. Doctors should ask patients about the use of herbal products, and patients should volunteer the information if a doctor does not ask as an important safety precaution. In addition, patients may discuss concerns with their pharmacist.

As reported in a recent study published in the November issue of Pharmacy & Therapeutics, an aspirin a day can take away the gastrointestinal (GI) safety advantage of selective COX-2 inhibitors over traditional nonsteroidal anti-inflammatory (NSAID). Eight out of ten patients who have NSAID GI complications have no prior symptoms, so both doctor and patient need to be aware of all possibilities.

Researchers Mark Fendrick, MD, University of Michigan, and colleagues suggest the following:

For patients who are not taking aspirin:
- Those with a low or no GI risk should use a traditional NSAID.
- Those with a high GI risk should use a selective COX-2 inhibitor.

Dr. Fendrick explains that selective COX-2 inhibitors may be a safer strategy for people with low or no GI risk who are not taking aspirin, but the COX-2 drugs are much more expensive. In summary, the extra cost may not be worth it for these people at low risk.

He says that unrestricted use of coxibs for people with GI risk factors is a worthwhile added expenditure, according to an economic analysis test.

For patients who are taking aspirin for cardiovascular prophylaxis:
- Those with a low or no GI risk should use a traditional NSAID plus a proton pump inhibitor or a gastroprotective agent (such as misoprostol -- Cytotec®, Searle) to help protect the GI tract. Misoprostol is rarely prescribed in the U.S. or Canada because it must be taken four times a day and causes diarrhea in about one third of patients; thus, making it a more difficult drug treatment.
- Those with a high GI risk must use either a proton pump inhibitor or gastroprotective agent plus either a traditional NSAID or selective COX-2 inhibitor.

There is no data comparing a traditional NSAID with a selective COX-2 inhibitor in these patients, so Dr. Fendrick suggests that the choice of drug be made after the trade-off is assessed between perceived GI safety over the added costs of the selected medication.

In the rare case of people who have experienced previous GI bleeding, the combination of a COX-2 and a proton pump inhibitor is recommended at this time by researchers in this study, although conclusive evidence is not yet available.

The researchers say that aspirin in combination with any NSAID (traditional or selective) increases the risk of GI complications. They also conclude that economics play a critical role in the choice of NSAID in patients receiving gastroprotection -- "until the added benefits of selective agents are established, a traditional NSAID seems reasonable from a cost-effective perspective."

Montreal, QC -- Acetaminophen (TYLENOL) is often recommended for initial use in osteoarthritis and other forms of arthritis because of its GI safety and low cost. But according to a recent study, elderly patients taking high doses of acetaminophen have higher rates of gastrointestinal (GI) events than those using lower doses of the drug. Dr. Elham, Rahme from the McGill University in Montreal, Quebec and colleagues published their findings in a recent issue of Arthritis & Rheumatism.

Results: The researchers examined rates of adverse GI events in 21,000 elderly patients treated with acetaminophen and 26,000 taking a nonsteroidal anti-inflammatory (NSAID). Patients taking higher doses of acetaminophen (over 2600 mg/day) had higher rates of GI adverse events compared with those taking lower doses. When the figures were adjusted for GI "risk susceptibility", those taking high-dose acetaminophen had similar rates of GI events as those did taking high-dose NSAIDs.

Dr. Steven B. Abramson from the New York University School of Medicine was not one of the researchers in this study, but offers the following information in reviewing the study's results: "What cannot be concluded from the study is that acetaminophen use is associated with more serious GI adverse events, such as ulcer and ulcer complications."