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PRIORITY PRESS - 73rd Annual Meeting of the American College of Rheumatology

Philadelphia, Pennsylvania / October 17-21, 2009

New criteria have been proposed for the clinical diagnosis of fibromyalgia (FM) which do not rely on tender point assessment but which correlate very highly with diagnostic criteria established in 1990 by the American College of Rheumatology (ACR) and which should facilitate diagnosis of the condition in the primary care setting.

In 1990, an ACR committee under lead author Dr. Frederick Wolfe, National Data Bank, Wichita, Kansas, indicated that patients with widespread pain in combination with tenderness at 11 or more of 18 specific tender point sites met the criteria for FM (Arthritis Rheum 1990;33:160-72). However, as Dr. Wolfe told delegates here, these criteria are not always used correctly by primary care practitioners.

“Primary care physicians do not know how to do tender point counts for the most part,” he added, “and we believe that FM is a de facto symptom-based diagnosis in primary care.” Similarly concerned that the ACR criteria do not take into account other important symptoms of FM including fatigue, sleep disturbances and cognitive difficulties, the new committee sought to identify non-tender point clinical diagnostic criteria for FM as well as a symptom severity scale to assess the impact of the condition on quality of life.

To that end, members carried out a two-stage, 55-site multicentre study involving 1002 FM patients and pain controls. “Physicians performed detailed interviews and physical exams, including the tender-point exam,” Dr. Wolfe reported, “and widespread pain was assessed using the 0 to 19 widespread pain index (WPI).” Importantly, patients in the study had already been diagnosed with FM prior to being enrolled in the study and the same physician who had made the diagnosis also undertook the trial evaluation.

As Dr. Wolfe indicated, the WPI emerged as the best predictor of FM but following exclusion of WPI scores, analyses also identified unrefreshed sleep, fatigue, cognitive difficulties and the extent of somatic symptoms as key predictors of FM. These four categorical symptom variables were then combined into a 0 to 12 Symptom Severity scale, which correlated highly with both the tender point count (r=0.688) and the WPI (r=0.733).

Based on these new sets of criteria, committee members indicated that patients meet the new diagnostic criteria for FM if their WPI score is 7 or higher and their symptom severity score is 5 or higher, or if their WPI is between 3 and 6 and their symptom severity score is 9 or higher; patients must also have experienced their symptoms persistently for at least three months, Dr. Wolfe added.

When they compared ACR classification criteria for FM, committee members found that the new criteria correctly identified 80.9% of ACR diagnosed cases of FM, while physician diagnoses agreed with ACR criteria in 84.1% of cases. Furthermore, the new diagnostic criteria agreed with a symptom severity scale of 7 or greater in 93% of cases, Dr. Wolfe noted. He told delegates that in the second phase of the study, a simple categorical form, suitable for use in the clinic, performed as well as phase I variables.

“We have proposed simple clinical criteria for FM that do not require the use of tender points and these criteria expand the definition of FM to include symptoms other than pain and provide a measure to assess FM symptom-related severity,” Dr. Wolfe and colleagues concluded. They stressed that they were not suggesting that the new criteria replace ACR criteria but in settings where tender point counts are not feasible, the proposed criteria might be more applicable in clinical or research settings.

Other Common Symptoms

Pain might be the predominant symptom in FM but treatment should improve other common symptoms as well for a better overall response. To measure a treatment’s global effects, Dr. Lesley Arnold, Professor of Psychiatry and Director, Women’s Health Research, University of Cincinnati College of Medicine, Ohio, and colleagues set out to develop an FM Responder Index by analyzing pooled trial data to determine what symptom domains drive patient perception that they are improving. A total of 1664 patients were included in the analysis and treatment groups included those who received pregabalin 300 mg/day, 450 mg/day or placebo.

As the authors reported, improvement in Patient Global Improvement Change (PGIC) best correlated with improvements in pain, fatigue, sleep disturbances and physical function. “Pain remains the main focus of our outcome measures and that makes sense because FM is primarily a pain condition,” Dr. Arnold confirmed. “But we also recognize that patents experience other symptoms that can be disabling as well, so the key outcomes that we are going to focus on as we move to improve our treatment of FM are pain, fatigue, sleep problems and physical function.”

Given the wide spectrum of symptoms that characterize the condition, a variety of medications is used to treat FM, including duloxetine, gabapentin, tricyclic antidepressants, tramadol and hydrocodone. The analgesic pregabalin was the first approved treatment for FM in the US and Canada. In one short-term observational study comparing pregabalin (n=68) to standard-of-care (n=18), Dr. Micha Abeles, University of Connecticut School of Medicine, Farmington, and colleagues initially reported that approximately 50% of patients in both arms responded to treatment in the short-term but discontinuation rates were high for both treatment groups.

In order to assess persistency of treatment benefit, patients who responded to pregabalin or to standard-of-care medications in the original short-term trial were continued on the same treatment. Pregabalin was initiated at a dose of 75 mg b.i.d. and titrated up to a maximum of 300 mg b.i.d. as tolerated but patients could remain on previous medications. For this study, standard-of-care was defined as a physician’s routine approach to treatment of FM. The visual analog scale (VAS), the total FM impact questionnaire (FIQ) score and the PGIC were used to assess response to treatment at the end of one year. As investigators noted, response was considered to be clinically meaningful if there was a 30% or greater improvement from baseline on either the VAS or the FIQ.

At one year, 16 out of 18 patients who remained on pregabalin out to one year had persistent benefit compared with six out of 16 patients in the comparator arm. “Our original observational study was designed to obtain real-world experience with pregabalin and compare it to conventional therapies to assess its position in the therapeutic armamentarium,” Dr. Abeles explained. “But the take-home message from this longer-term study suggests that once patients respond to pregabalin and can tolerate it, this would be the drug you need to consider because none of the other drugs that are being utilized for FM work for long periods of time.”

Treatment-refractory Pain

Here at the ACR, lead author Dr. Brett Stacey, Oregon Health & Science University, Portland, reported results on results of an analysis evaluating a subset of patients with treatment-refractory pain. Twenty-five patients were included in the analysis, 24 of whom were refractory to gabapentin and the tricyclics. Investigators sought to determine the long-term safety and efficacy of pregabalin 150-600 mg/day in these patients. At any time during the study, 40% of patients received a tricyclic antidepressant, 40% received gabapentin and 88% received a third-line medication concomitantly. The first 15 months of the study included three-month treatment cycles, followed by a three- to 28-day drug holiday that lasted until relapse occurred.

Nineteen patients completed the 15-month study. At baseline, 71% of patients reported severe pain (70 mm or more on the Short-Form McGill Pain Questionnaire VAS). At the end of 15 months, only 38% of patients reported the same severity of pain, while a 30% or greater reduction in mean pain scores from baseline to month three was reported by 54.2% of the group and from baseline to study end point by 45.8% of patients. Moreover, a 50% or greater reduction in mean pain scores from baseline to month 3 was reported by half of the group and by 37.5% of the group from baseline to study end point. Pregabalin was generally well tolerated, as few patients discontinued due to adverse events, the authors noted. Results suggested that this particular medication might be helpful for patients who do not achieve a satisfactory response to other medications used to treat FM.

Summary

A wide variety of medical strategies are used to treat FM but none appear to have persistent benefit. New findings suggest the first approved analgesic for FM pregabalin can have longer-lasting effects in responders and that it may be beneficial for patients who have treatment-refractory pain.