Osteoarthritis is extremely prevalent and results in significant costs, both financial and quality of life, for those that suffer from the debilitating disease. The OPTION trial was designed to evaluate the efficacy and safety of Natural Eggshell Membrane as a treatment option for osteoarthritis. Our preliminary study indeed proved NEM® both effective and safe for treating pain and stiffness associated with OA of the knee. NEM® has the added benefit of avoiding the concerning side effects associated with long-term use of other OA treatments such as NSAIDs.
Patients experienced a relatively rapid (10 days) response for all WOMAC scores with a mean response of approximately 15% (12.8% to 15.9%). By the end of the follow-up period (60 days), the mean response remained approximately 15% (13.5% to 15.4%) for all WOMAC scores except stiffness which was 26.6%. While this is superior to the response shown for glucosamine and chondroitin in previous clinical investigations [12
], it failed to reach the expected 35% response rate employed in the clinical design. Despite this shortcoming, the results were shown to be statistically significant. The safety profile for NEM® is also of significance as there are no known side effects, excluding the obvious egg allergy concern. This is of obvious importance in a condition that requires long-term treatment. Significant and sometimes serious side effects associated with other OA treatments frequently limits treatment options.
The measure of subjective symptoms (i.e., pain, stiffness, etc.) of arthritis and the wide variation in individual patient’s perception of these symptoms results in complex relationships that can be difficult to elucidate from the reporting of mean treatment effects in clinical trials and may fail to adequately describe the potential benefits to the individual patient [28
Number Needed to Treat (NNT) is a form of responder analysis and is a widely accepted and statistically valid measure of treatment effect [32
]. NNTs of 5 or below are generally accepted as equating to an effective treatment for pain-related conditions [30
]. In order to perform an NNT evaluation of the OPTION data, a treatment response rate table was prepared for the treatment and placebo groups at all time points for the pain (see Table ) and stiffness (not shown) WOMAC subscales. It becomes evident that there are response rates that are quite likely to be clinically relevant (i.e., ≥30% reduction from baseline). For example, approximately one-third (33%) of study subjects experienced greater than 30% reduction in pain at 10 days, with a similar number of subjects (32%) having experienced greater than 50% reduction in pain at 60 days. In both instances, this rate was more than two times (~2.5×) that of the placebo group. Approximately one-quarter (25%) of study subjects experienced greater than 50% reduction in stiffness at 10 days, with the number of patients increasing to more than one-half (53%) having experienced this level of improvement at 60 days. The 10-day result was more than two times (~2.5×) that of the placebo group and the 60-day result was nearly five times (~4.8×) that of placebo.
Percent of patients experiencing reduction in pain from Baseline at 10, 30, and 60 days post-treatment
These various responder rates were then converted to NNT values which include 95% confidence intervals (95% CI) according to the method described by Wen et al. [33
]. NNT values were determined for each level of improvement (as shown in Table ) for both pain and stiffness. At 10, 30, and 60 days, NNTs for at least 50% reduction in pain were 28.0 (95% CI, 26.2 to 29.8), 5.6 (3.9 to 7.4), and 5.0 (3.1 to 6.9), respectively. In clinical practice, one out of every five patients should experience at least a 50% reduction in pain within 30–60 days. By comparison, we determined an NNT of 23.8 (95% CI, 15.2 to 32.4) from the GAIT data for a 50% reduction in WOMAC pain scores for the overall study population [12
]. A similar 50% reduction in rheumatoid arthritis pain was reported as 4 in a review of three clinical trials for adalimumab, etenercept, and double-dose infliximab [34
NNT values were also determined for 50% reduction in stiffness at each time point. We obtained NNTs of 6.5 (95% CI, 4.6 to 8.4), 7.9 (6.1 to 9.7), and 2.4 (0.5 to 4.3) at 10, 30, and 60 days, respectively. This demonstrates that there is a clinically relevant reduction in stiffness at all time points during the study. This is particularly true at 60 days where nearly one out of every two patients would experience a 50% reduction in stiffness.
With one-third of those 65 and older having been diagnosed with osteoarthritis [1
], and that number expected to grow immensely as the overall US population ages, it is important for patients to have treatment options that are both effective and safe. The reporting of the results from the OPTION trial provides this needed treatment option.
The trial suffered from a number of issues. The limited initial enrollment (67 subjects), the relatively high drop-out rate (43%), and the smaller mean treatment effect than anticipated (15% versus 35%) could have compromised the statistical significance of the trial results. In addition to these inherent limitations, combined they also prevented post hoc analysis of subgroups of patients, say by severity of disease. Less stringent requirements for concomitant pain treatment or a more liberal rescue pain policy may have reduced the drop-out rate considerably. The inclusion of a comparative treatment agent may have provided additional information, but would have required a significantly larger study population. A larger follow-up study with some modifications may allow us to better determine which patients are most helped by NEM® supplementation.