ROME – Combined intra-articular injections of Tr14 (Traumeel) and Ze14 (Zeel) provided statistically significant, clinically relevant, and long-lasting relief of knee osteoarthritis pain in a phase III, randomized, double-blind, placebo-controlled trial.
The size of the effect was consistent with that seen for other pain-relieving drugs used to manage knee osteoarthritis (OA), including intra-articular (IA) injections of hyaluronic acid and corticosteroids, and even oral administration of diclofenac, the study investigators reported.
“From a qualitative perspective, the risk-benefit relationship for Tr14&Ze14 appears favorable, particularly compared to oral NSAIDs,” noted Dr. Carlos Lozada and his associates in a poster presentation at the European Congress of Rheumatology.
Dr. Lozada of the University of Miami noted in an interview that, unlike oral NSAIDs, the safety profile of Tr14&Ze14 was “benign, with no signals of cardiovascular, gastrointestinal, or other concerning risks,” which might offer an advantage for patients who are unable to take NSAIDs but still need something to provide OA pain relief.
According to their individual prescribing information, Tr14 and Ze14 are two homeopathic medicines available for the management of various musculoskeletal disorders and, in combination, for inflammatory and degenerative conditions such as OA. They each contain 14 different components, such as arnica, belladonna, echinacea, and comfrey root, and can be given by subcutaneous, intradermal, intramuscular, IA, or intravenous administration.
The MOZART (Study of Intra-articular Injections vs. Placebo in Patients With Pain From Osteoarthritis of the Knee) trial was conducted at 30 clinical study sites in the United States and involved 232 patients with moderate to severe pain associated with knee OA. Patients were randomized to weekly IA injections of Tr14&Ze14 for 3 weeks or to intra-articular placebo injections.
The main results were presented at the annual meeting of the American College of Rheumatology in Boston last year (Arthritis Rheumatol. 2014;66:S1266[Abstr. 2896]) and showed that significantly improved knee OA pain – assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale – was achieved after 8 days with Tr14&Ze14 vs. IA placebo injections.
The current analysis looked at the size of the effect achieved using the Hedges’ g* statistical method, which is a calculation based on the difference between treatment means, divided by the estimated common standard deviation, and then multiplied by a correlation factor that adjusts for sample sizes. Comparing the size of the effect seen with Tr14&Ze14 vs. IA placebo injections for the WOMAC pain subscale over time showed a consistent pain-relieving benefit of 0.26 at 15 days’ assessment, 0.22 at 29 days, 0.30 at 43 days, 0.31 at 57 days, 0.30 at 71 days, 0.25 at 85 days, and 0.25 at 99 days, the final assessment point in the study.
These effect sizes were then compared with those seen with other treatments used for OA pain relief obtained from a recent meta-analysis of 129 trials (Ann. Intern. Med. 2015;162:46–54). In that meta-analysis, IA administration of anti-inflammatory medicines was found to be superior to oral NSAIDs for the relief of pain. While this may partly do due to an integrated placebo effect of having injections, small but robust differences were seen between the active treatments, the meta-analysis’ authors concluded.
Using IA placebo injections as the comparator, the meta-analysis found that the Hedges’ g* effect sizes at 3 months were 0.34 for IA injections of hyaluronic acid and 0.32 for IA injections of corticosteroids. Effect sizes for commonly used oral NSAIDs were 0.23 for diclofenac, 0.15 for ibuprofen, 0.09 for naproxen, and 0.04 for celecoxib.
Dr. Lozada noted that while the current trial data showed that a consistent and long-lasting pain-relieving effect could be achieved following just three weekly IA injections of Tr14&Ze14, they cannot provide information on when to re-treat patients.
“One reason the follow up was for 99 days was to try to get some notion of how long the effect would last,” he said. “It doesn’t answer the question at this point on when you have to re-treat, I think that will still have to be individualized according to the patient.”
The study was sponsored by Biologische Heilmittel Heel GmbH. Dr. Lozada is a consultant for Rio Pharmaceutical Services and Heel Inc.