Wednesday July 30 2008
The drug is based on an extract from the Indian frankincense plant (Boswellia serrata)
“Frankincense, a wise man’s remedy for arthritis” is the headline in the Daily Mail. Capsules of frankincense extract were found to relieve symptoms of osteoarthritis within a week, and by three months stiffness and pain had reduced by up to two thirds with no side effects, the newspaper reports.
This is reportedly the first trial of the drug 5-Loxin, an extract from the plant used to make frankincense, and it provides promising results. However, the results should be considered preliminary. Further research is needed in larger numbers of people for longer periods of time to confirm efficacy and safety. The drug will need to be compared with the wide range of other medical and surgical treatments currently used in the treatment of osteoarthritis, and any possible role of this treatment in arthritic conditions other than osteoarthritis will need to be investigated.
Where did the story come from?
Krishanu Sengupta of the Cellular and Molecular Biology Division, Laila Impex R&D Center, Vijayawada, India, and colleagues, carried out this research. The study was funded by the Laila Impex R&D Center. Laila Impex is the company that makes 5-Loxin. This was an open-access study published in the peer-reviewed medical journal Arthritis Research & Therapy.
What kind of scientific study was this?
This was a double-blind randomised controlled trial designed to assess the efficacy and safety of 5-Loxin for osteoarthritis of the knee. The 5-Loxin treatment is a gum extract of the ancient herb Boswellia serrata (also called Indian frankincense), which is enriched with other chemicals to create a compound that inhibits the enzyme 5-lipoxygenase, which is known to be a key enzyme in the inflammatory process.
The trial was carried out in India between July and October 2006, and 75 people with mild-to-moderate osteoarthritis of the knee were randomised to receive either 100mg (low dose) or 250mg (high dose) of 5-Loxin per day, or identical placebo capsules. Some 236 outpatients were originally selected based on symptoms and signs of osteoarthritis. To be included in the trial, people had to have been suffering knee pain for longer than three months, be between 40 and 80 years old, and score between 4 and 7 on a 10-point visual analogue pain scale once they had stopped taking their usual medication (daily anti-inflammatory drugs or paracetamol) for one week. The researchers excluded all those with inflammatory conditions, such as rheumatoid arthritis, gout, knee injury, need for steroid injection in the past three months, obese people, those with high alcohol intake, or those with medical conditions that may put them at risk from the treatments (e.g. liver or kidney conditions).
The patients completed a baseline questionnaire about their medical history and nutritional status. They were followed up at seven, 30, 60 and 90 days. Pain, stiffness and physical function scores were assessed at each visit, and blood tests for inflammatory markers and urine samples were taken. Based on pain scores, the patients could receive “rescue” anti-inflammatory drugs if they were needed. If these were taken, the patients were advised to discontinue taking the “rescue” treatment three days before each assessment. No other treatments were taken.
At baseline and 90 days, the patients had fluid taken from the knee joint to look at the concentration of matrix metalloproteinase-3 (MMP3) – an enzyme which can break down bone cartilage. Adverse effects were self-reported by the patients. The primary outcome for the study was the difference in pain, stiffness and physical function with 5-Loxin compared with the placebo.
What were the results of the study?
Seventy patients completed the study. There was significant improvement in pain score with both low- and high-dose 5-Loxin compared with the placebo. Compared with the placebo, low-dose 5-Loxin improved pain score by 49%, 24% and 40% on the three different scales used. However, the 43% improvement in stiffness and 29% improvement in function were not significant when compared with the placebo. In the high-dose group, percentage improvements were greater compared with the placebo across all measures of pain, stiffness and function, and these were significant. Both dose groups showed significant improvement in pain at one week compared with the placebo.
There was no change in MMP3 concentration in the fluid from the knee in the placebo group. However, 5-Loxin significantly reduced MMP3 concentration (by 31% at the low dose and 46% at the high dose). The reduction in MMP3 with high-dose 5-Loxin was also significantly greater than with the low dose. There was no difference in adverse effects seen in the treatment or control groups.
What interpretations did the researchers draw from these results?
The researchers conclude that 5-Loxin is safe and significantly reduces pain and improves physical functioning in people with osteoarthritis.
What does the NHS Knowledge Service make of this study?
This is reportedly the first trial of the drug 5-Loxin, and it provides promising results. However, results should be considered preliminary. There are a number of limitations to the interpretation of this study:
- This trial was relatively small, and this may have affected the ability of randomisation to balance the groups for important characteristics. For example, on average those in the high-dose 5-Loxin group were about 6kg lighter, and had a BMI about 3.5 units lower, than those in the other groups.
- The method of how participants were randomly assigned into groups was not described, and some methods of randomisation are not as robust as others.
- The placebo pills were described as being “similar” in appearance, colour and taste to the 5-Loxin pills, but it is not clear if they were similar enough to prevent participants guessing which treatment they were receiving.
- The trial was relatively short. Longer trials will be needed to confirm long-term safety.
In order to confirm efficacy and safety results, further research is needed in larger numbers of people for longer periods of time. Research is also required for people with different characteristics (strict inclusion and exclusion criteria were used here), and for those with osteoarthritis of joints other than the knee. Efficacy compared with the wide range of other medical and surgical treatments used in the treatment of osteoarthritis will also be needed. The possible role of this treatment in arthritic conditions aside from osteoarthritis is not known from this research.
Sir Muir Gray adds...
One trial is rarely conclusive; more data are needed.