There’s an important clinical trial that has just wrapped up phase II that should be of interest to anyone who has Fibromyalgia. Dr. William Pridgen and Associate Professor Carol Duffy at the University of Alabama have been experimenting with the use of Famvir, an anti-viral drug that is commonly used for the treatment of Herpes Simplex, combined with Celebrex, a COX-2 inhibitor, as a method of treating Fibromyalgia.
After watching many of his patients struggle with gastrointestinal
issues for decades, Dr. Pridgen gave several patients Famvir on a hunch. He figured that if the GI symptoms intensified during periods of increased stress, a virus could possibly be to blame. Professor Duffy had previously isolated the herpes simplex- I virus in the GI tracts of Fibromyalgia patients. Dr. Pridgen used Duffy’s work to guide his treatment of these FM patients. Although the patients’ symptoms improved, Dr. Pridgen felt that there must be a second drug that would provide a better result if added to the Famvir. He added Celebrex, and found that many patients responded more favorably to this combination.
Here is Dr. Pridgen’s description of the method he is using to test this hypothesis- that the combination of Famvir (famciclovir) and Celebrex (celecoxib) will result in a significant decrease in Fibromyalgia symptoms:
A total of 143 patients selected using the ACR 2010 FM criteria were enrolled at 12 sites in a 16-week, double-blind, placebo-controlled trial. Patients were randomized (1:1) to receive a proprietary combination of celecoxib + famciclovir or placebo. Outcome measures included a 24-hour recall pain numeric rating scale (NRS), Fibromyalgia Impact Questionnaire (FIQ-R), Patient Global Impression of Change (PGIC), and the PROMIS fatigue short form at baseline, and after 6, 12 and 16 weeks of study participation.
Here are Dr Pridgen’s results:
The primary efficacy endpoint was change in pain from baseline. Pain reduction was evaluated using the pain NRS and the 7-day recall pain item from the FIQ-R. Change from baseline was determined using an MMRM approach with LOCF/ BOCF imputation for missing data. A significant decrease in pain was observed for patients on treatment vs. placebo at 16 weeks by both measures. The absolute change on the NRS was -1.9 units vs -1.1, comparing active to placebo (p=0.031). On the FIQ-R item, the change was -2.2 vs -0.92 (p=0.001). Key secondary endpoints included analysis of the PGIC, where a value of “1” or “2” was considered a clinical responder. Significantly improved PGIC response rates were noted at endpoint: 33.3% for active vs 19.2% in placebo patients (p=0.031). Total FIQR score change at the endpoint visit was -17.54 vs -7.87 (p=0.002), while changes in the 3 domains were 14.29 vs -5.44 (p=0.004) for Function, -4.29 vs -1.89 (p=0.003) for Overall Impact, and -16.77 vs -7.90 (p=0.004) for Symptoms. In addition, improvements in fatigue were seen at endpoint on the PROMIS fatigue (-7.62 units vs -4.15; p=0.020).
The safety profile was especially encouraging. Despite the celecoxib component, gastrointestinal and nervous system treatment emergent adverse events were reported significantly more often in the placebo treatment group (GI: 29.0% vs 42.5%; nervous system: 17.4% vs 23.3%; active to placebo), and study completion rates favored active treatment over placebo (82.6% vs. 60.8%) (largely driven by higher placebo discontinuation rates due to adverse events and lack of efficacy).
In short, Dr. Pridgen used two different methods to track patients pain. He used a Numeric Rating Scale (NRS), which is the 0-10 scale that so many of us are so familiar with. He also used The Revised FM Impact Questionnaire (FIQR) to assist patients in reporting their pain levels. This questionnaire requires patients to respond to a variety of statements such as, “[How difficult is it to] Change sheets on bed,” on a scale that ranges from No Difficulty to Very Difficult. Both systems showed a significant decrease in symptoms following treatment with both Famvir and Celebrex.
In an article written by the University of Alabama, Dr Pridgen stated,
The patients who took both drugs, however, came back and said everything was better. Their fibromyalgia was gone. Their chronic fatigue was gone. Their headaches were gone. All of these things had cleared up. When the first few patients approached him, he thought it was a fluke, but as more and more and more patients said the same thing, he knew it couldn’t be a coincidence.
Here are Dr. Pridgen’s conclusions from his Phase-IIa trials:
A proprietary combination of famciclovir, which we postulate is inhibiting herpesvirus replication, and celecoxib, known to inhibit both herpesvirus replication and reactivation, was efficacious in treating multiple symptoms of FM. Given the simultaneous improvement in many domains and the surprising tolerability of this combination of drugs, we believe this combination warrants further study as a potential new therapy for fibromyalgia patients.