Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: Results of a randomized,double‐blind,placebo‐controlled trial

Objective

To assess the efficacy and safety of milnacipran at a dosage of 100 mg/day (50 mg twice daily) for monotherapy treatment of fibromyalgia.

Methods

A double‐blind, placebo‐controlled trial was performed to assess 1,025 patients with fibromyalgia who were randomized to receive milnacipran 100 mg/day (n = 516) or placebo (n = 509). Patients underwent 4–6 weeks of flexible dose escalation followed by 12 weeks of stable‐dose treatment. Two composite responder definitions were used as primary end points to classify the response to treatment. The 2‐measure composite response required achievement of ≥30% improvement from baseline in the pain score and a rating of “very much improved” or “much improved” on the Patient's Global Impression of Change (PGIC) scale. The 3‐measure composite response required satisfaction of these same 2 improvement criteria for pain and global status as well as improvement in physical function on the Short Form 36 (SF‐36) physical component summary (PCS) score.

Results

After 12 weeks of stable‐dose treatment, a significantly greater proportion of milnacipran‐treated patients compared with placebo‐treated patients showed clinically meaningful improvements, as evidenced by the proportion of patients meeting the 2‐measure composite responder criteria (P < 0.001 in the baseline observation carried forward [BOCF] analysis) and 3‐measure composite responder criteria (P < 0.001 in the BOCF). Milnacipran‐treated patients also demonstrated significantly greater improvements from baseline on multiple secondary outcomes, including 24‐hour and weekly recall pain score, PGIC score, SF‐36 PCS and mental component summary scores, average pain severity score on the Brief Pain Inventory, Fibromyalgia Impact Questionnaire total score (all P < 0.001 versus placebo), and Multidimensional Fatigue Inventory total score (P = 0.036 versus placebo). Milnacipran was well tolerated by most patients, with nausea being the most commonly reported adverse event (placebo‐adjusted rate of 15.8%).

Conclusion

Milnacipran administered at a dosage of 100 mg/day improved pain, global status, fatigue, and physical and mental function in patients with fibromyalgia.

     

Attentional functioning in fibromyalgia,rheumatoid arthritis,and musculoskeletal pain patients

Objectives

To investigate whether chronic pain patients have deficits in attentional functioning compared with pain‐free controls, and whether fibromyalgia patients have larger deficits in attentional functioning compared with rheumatoid arthritis and musculoskeletal pain patients.

Methods

Sixty patients (20 in each of 3 patient groups) and 20 pain‐free controls completed measures assessing pain intensity, mood, pain‐related disability, somatic awareness, and catastrophic thinking about pain. Attentional functioning was assessed using an age‐standardized, ecologically valid test battery. Analyses were made of between‐group differences.

Results

Sixty percent of patients had at least one score in the clinical range of neuropsychological impairment, independent of demography and mood. Fibromyalgia patients were more anxious and somatically aware than rheumatoid arthritis or musculoskeletal pain patients, but did not show larger attentional deficits than other patient groups.

Conclusion

All 3 groups of chronic pain patients, regardless of diagnosis, had impaired cognitive functioning on an ecologically sensitive neuropsychological test of everyday attention.

     

A randomized,double‐blind,placebo‐controlled trial of pramipexole,a dopamine agonist,in patients with fibromyalgia receiving concomitant medications

Objective

To assess the efficacy and safety of pramipexole, a dopamine 3 receptor agonist, in patients with fibromyalgia.

Methods

In this 14‐week, single‐center, double‐blind, placebo‐controlled, parallel‐group, escalating‐dose trial, 60 patients with fibromyalgia were randomized 2:1 (pramipexole:placebo) to receive 4.5 mg of pramipexole or placebo orally every evening. The primary outcome was improvement in the pain score (10‐cm visual analog scale [VAS]) at 14 weeks. Secondary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ), the Multidimensional Health Assessment Questionnaire (MDHAQ), the pain improvement scale, the tender point score, the 17‐question Hamilton Depression Inventory (HAM‐d), and the Beck Anxiety Index (BAI). Patients with comorbidities and disability were not excluded. Stable dosages of concomitant medications, including analgesics, were allowed.

Results

Compared with the placebo group, patients receiving pramipexole experienced gradual and more significant improvement in measures of pain, fatigue, function, and global status. At 14 weeks, the VAS pain score decreased 36% in the pramipexole arm and 9% in the placebo arm (treatment difference –1.77 cm). Forty‐two percent of patients receiving pramipexole and 14% of those receiving placebo achieved ≥50% decrease in pain. Secondary outcomes favoring pramipexole over placebo included the total FIQ score (treatment difference –9.57) and the percentages of improvement in function (22% versus 0%), fatigue (29% versus 7%), and global (38% versus 3%) scores on the MDHAQ. Compared with baseline, some outcomes showed a better trend for pramipexole treatment than for placebo, but failed to reach statistical significance, including improvement in the tender point score (51% versus 36%) and decreases in the MDHAQ psychiatric score (37% versus 28%), the BAI score (39% versus 27%), and the HAM‐d score (29% versus 9%). No end points showed a better trend for the placebo arm. The most common adverse events associated with pramipexole were transient anxiety and weight loss. No patient withdrew from the study because of inefficacy or an adverse event related to pramipexole.

Conclusion

In a subset of patients with fibromyalgia, ∼50% of whom required narcotic analgesia and/or were disabled, treatment with pramipexole improved scores on assessments of pain, fatigue, function, and global status, and was safe and well‐tolerated.

     

Evaluation of the efficacy and safety of terguride in patients with fibromyalgia syndrome: Results of a twelve‐week,multicenter, randomized,double‐blind,placebo‐controlled,parallel‐group study

Objective

To assess the efficacy and safety of terguride, a partial dopamine agonist, in patients with fibromyalgia syndrome (FMS).

Methods

In a 12‐week, multicenter, double‐blind, placebo‐controlled, parallel‐group study, 99 patients were randomized at a ratio of 2 to 1 to receive terguride or placebo. Over 21 days, the dosage was titrated to a maximum daily dose of 3 mg of terguride or placebo, and this fixed dosage was continued over 9 weeks. The primary efficacy variable was the intensity of pain (100‐mm visual analog scale). Secondary efficacy variables included the Fibromyalgia Impact Questionnaire (FIQ) score, the tender point score (TPS), and the Hamilton Depression Scale (HDS) score. During the study, patients were evaluated for the presence of cervical spine stenosis by magnetic resonance imaging (MRI).

Results

No significant differences in the change in pain intensity, FIQ score, TPS, or HDS score between baseline and 12 weeks were observed in the terguride group as compared with the placebo group. Cervical spine stenosis was detected in 22% of the patients. Only patients with cervical spine stenosis responded to terguride treatment. FIQ scores improved significantly (per‐protocol analysis), and pain intensity, the TPS score, and the HDS score showed a trend toward improvement in the terguride group as compared with the placebo group. Terguride treatment was safe. Only those adverse events already known to be side effects of terguride were observed. Premature termination of the study in patients receiving terguride (26%) occurred predominantly during up‐titration and in the absence of comedication for treatment of nausea.

Conclusion

Terguride treatment did not improve pain, the FIQ score, the TPS, or the HDS score in the total study population. However, a subgroup of patients with cervical spine stenosis seemed to benefit from terguride treatment.

     

A double‐blind,multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder

Objective

To assess the efficacy and safety of duloxetine, a serotonin and norepinephrine reuptake inhibitor, in subjects with primary fibromyalgia, with or without current major depressive disorder.

Methods

This study was a randomized, double‐blind, placebo‐controlled trial conducted in 18 outpatient research centers in the US. A total of 207 subjects meeting the American College of Rheumatology criteria for primary fibromyalgia were enrolled (89% female, 87% white, mean age 49 years, 38% with current major depressive disorder). After single‐blind placebo treatment for 1 week, subjects were randomly assigned to receive duloxetine 60 mg twice a day (n = 104) or placebo (n = 103) for 12 weeks. Co–primary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ) total score (score range 0–80, with 0 indicating no impact) and FIQ pain score (score range 0–10). Secondary outcome measures included mean tender point pain threshold, number of tender points, FIQ fatigue, tiredness on awakening, and stiffness scores, Clinical Global Impression of Severity (CGI‐Severity) scale, Patient Global Impression of Improvement (PGI‐Improvement) scale, Brief Pain Inventory (short form), Medical Outcomes Study Short Form 36, Quality of Life in Depression Scale, and Sheehan Disability Scale.

Results

Compared with placebo‐treated subjects, duloxetine‐treated subjects improved significantly more (P = 0.027) on the FIQ total score, with a treatment difference of −5.53 (95% confidence interval −10.43, −0.63), but not significantly more on the FIQ pain score (P = 0.130). Compared with placebo‐treated subjects, duloxetine‐treated subjects had significantly greater reductions in Brief Pain Inventory average pain severity score (P = 0.008), Brief Pain Inventory average interference from pain score (P = 0.004), number of tender points (P = 0.002), and FIQ stiffness score (P = 0.048), and had significantly greater improvement in mean tender point pain threshold (P = 0.002), CGI‐Severity (P = 0.048), PGI‐Improvement (P = 0.033), and several quality‐of‐life measures. Duloxetine treatment improved fibromyalgia symptoms and pain severity regardless of baseline status of major depressive disorder. Compared with placebo‐treated female subjects (n = 92), duloxetine‐treated female subjects (n = 92) demonstrated significantly greater improvement on most efficacy measures, while duloxetine‐treated male subjects (n = 12) failed to improve significantly on any efficacy measure. The treatment effect on significant pain reduction in female subjects was independent of the effect on mood or anxiety. Duloxetine was safely administered and well tolerated.

Conclusion

In this randomized, controlled, 12‐week trial (with a 1‐week placebo lead‐in phase), duloxetine was an effective and safe treatment for many of the symptoms associated with fibromyalgia in subjects with or without major depressive disorder, particularly for women, who had significant improvement across most outcome measures.

     

Low‐dose naltrexone for the treatment of fibromyalgia: Findings of a small,randomized, double‐blind,placebo‐controlled,counterbalanced, crossover trial assessing daily pain levels

Objective

To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of low‐dose naltrexone on daily self‐reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue.

Methods

Thirty‐one women with fibromyalgia participated in the randomized, double‐blind, placebo‐controlled, counterbalanced, crossover study. During the active drug phase, participants received 4.5 mg of oral naltrexone daily. An intensive longitudinal design was used to measure daily levels of pain.

Results

When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking low‐dose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016). Low‐dose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep. Thirty‐two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during low‐dose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05). Low‐dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported.

Conclusion

The preliminary evidence continues to show that low‐dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well‐tolerated. Parallel‐group randomized controlled trials are needed to fully determine the efficacy of the medication.

     

Impact of fibromyalgia pain on health‐related quality of life before and after treatment with tramadol/acetaminophen

Objective

To assess health‐related quality of life (HRQOL) in patients with moderate‐to‐severe fibromyalgia pain compared with the general population, and to assess the relationship between pain severity and HRQOL before and after treatment with an analgesic.

Methods

Data were obtained from a randomized, double‐blind study of patients with moderate‐to‐severe fibromyalgia pain. Patients received either tramadol/acetaminophen or placebo 4 times/day as needed for 91 days. HRQOL was measured with the Short Form 36 Health Survey (SF‐36) and the Fibromyalgia Impact Questionnaire (FIQ). Baseline HRQOL scores were compared with a national sample of noninstitutionalized adults and a sample of patients with impaired HRQOL due to congestive heart failure. Patients with fibromyalgia were divided into tertiles by change in pain severity, and SF‐36 scores were compared across the tertiles. Mean changes in SF‐36 and FIQ scores were compared between treatment groups.

Results

Patients with fibromyalgia scored lower than the US norm on all SF‐36 scales (P < 0.0001) and lower than patients with congestive heart failure on most scales. More severe pain was associated with greater impairment of HRQOL compared with less severe pain (P < 0.0001). Patients in the highest tertile for improved pain severity had greater improvement in HRQOL scores than patients in the lower tertiles. Compared with patients who received placebo (n = 157), patients treated with tramadol/acetaminophen (n = 156) showed greater improvement on SF‐36 physical functioning, role physical, bodily pain, and physical summary scales, as well as FIQ scales for ability to do job, pain, and stiffness (P < 0.01).

Conclusion

Moderate‐to‐severe fibromyalgia pain significantly impairs HRQOL, and effective pain relief in these patients significantly increases HRQOL.

     

The effectiveness of pulsed electrical stimulation in the management of osteoarthritis of the knee: Results of a double‐blind,randomized, placebo‐controlled,repeated‐measures trial

Objective

To determine the effectiveness of subsensory, pulsed electrical stimulation (PES) in the symptomatic management of osteoarthritis (OA) of the knee.

Methods

This was a double‐blind, randomized, placebo‐controlled, repeated‐measures trial in 70 participants with clinical and radiographically diagnosed OA of the knee who were randomized to either PES or placebo. The primary outcome was change in pain score over 26 weeks measured on a 100‐mm visual analog scale (VAS). Other measures included pain on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), function on the WOMAC, patient's global assessment of disease activity (on a 100‐mm VAS), joint stiffness on the WOMAC, quality of life on the Medical Outcomes Study Short‐Form 36 (SF‐36) health survey, physical activity (using the Human Activity Profile and an accelerometer), and global perceived effect (on an 11‐point scale).

Results

Thirty‐four participants were randomized to PES and 36 to placebo. Intent‐to‐treat analysis showed a statistically significant improvement in VAS pain score over 26 weeks in both groups, but no difference between groups (mean change difference 0.9 mm [95% confidence interval −11.7, 13.4]). Similarly, there were no differences between groups for changes in WOMAC pain, function, and stiffness scores (−5.6 [95% confidence interval −14.9, 3.6], −1.9 [95% confidence interval −9.7, 5.9], and 3.7 [95% confidence interval −6.0, 13.5], respectively), SF‐36 physical and mental component summary scores (1.7 [95% confidence interval −1.5, 4.8] and 1.2 [95% confidence interval −2.9, 5.4], respectively), patient's global assessment of disease activity (−2.8 [95% confidence interval −13.9, 8.4]), or activity measures. Fifty‐six percent of the PES‐treated group achieved a clinically relevant 20‐mm improvement in VAS pain score at 26 weeks compared with 44% of controls (12% [95% confidence interval −11%, 33%]).

Conclusion

In this sample of subjects with mild‐to‐moderate symptoms and moderate‐to‐severe radiographic OA of the knee, 26 weeks of PES was no more effective than placebo.

     

Efficacy of celecoxib,a cyclooxygenase 2–specific inhibitor,in the treatment of ankylosing spondylitis: A six‐week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug

Objective

To evaluate the short‐term efficacy of celecoxib, a cyclooxygenase 2–specific inhibitor, in the treatment of ankylosing spondylitis (AS).

Methods

The study was a 6‐week randomized, double‐blind, placebo‐controlled trial with 3 treatment arms: placebo, ketoprofen 100 mg twice daily, and celecoxib 100 mg twice daily. Patients who had AS according to the modified New York criteria, without peripheral synovitis and with active disease (pain ≥40 mm on a 100‐mm visual analog scale [VAS] and an increase in pain of at least 30% after nonsteroidal antiinflammatory drug withdrawal) were eligible for study. Primary outcome measures were change in pain intensity (VAS) and change in functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI]).

Results

Of the 246 randomized patients, 76 were allocated to receive placebo, 90 ketoprofen, and 80 celecoxib. There were no statistically significant differences between treatment groups at study entry. During the 6 weeks of the study, the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group, with a trend in favor of celecoxib when the 2 active treatments were compared. The mean changes were −13 mm, −21 mm, and −27 mm (P = 0.006) for pain and 1, −6, and −12 (P = 0.0008) for BASFI score in the placebo, ketoprofen, and celecoxib groups, respectively. During treatment, the number of patients reporting epigastric pain was 6 (8%), 13 (14%), and 10 (13%) in the placebo, ketoprofen, and celecoxib groups, respectively.

Conclusion

The results of this study confirm the clinically relevant antiinflammatory effect of celecoxib at a 200‐mg daily dosage, with significant improvement of both pain and function in patients with AS.

     

Adalimumab in severe and acute sciatica: A multicenter,randomized, double‐blind,placebo‐controlled trial

Objective

Based on several experimental results and on a preliminary study, a trial was undertaken to assess the efficacy of adalimumab, a tumor necrosis factor α inhibitor, in patients with radicular pain due to lumbar disc herniation.

Methods

A multicenter, double‐blind, randomized controlled trial was conducted between May 2005 and December 2007 in Switzerland. Patients with acute (duration of <12 weeks) and severe (Oswestry Disability Index score of >50) radicular leg pain and imaging‐confirmed lumbar disc herniation were randomized to receive as adjuvant therapy either 2 subcutaneous injections of adalimumab (40 mg) at 7‐day intervals or matching placebo. The primary outcome was the score for leg pain, based on a visual analog scale (0–100 mm), which was recorded every day for 10 days and at 6 weeks and 6 months.

Results

Of the 265 patients screened, 61 were enrolled; 31 patients were assigned to receive adalimumab, and 4 patients in the placebo group were lost to followup. Over time, the course of leg pain was more favorable in the adalimumab group than in the placebo group (P = 0.002). However, the effect size was relatively small, and at the last followup visit the difference was 13.8 (95% confidence interval −11.5, 39.0). Compared with patients in the placebo group, approximately twice as many patients in the adalimumab group fulfilled the criteria for “responders” and for “low residual disease impact” (P < 0.05), and fewer surgical discectomies were performed (6 versus 13 in the placebo group; P = 0.04).

Conclusion

The addition of a short course of adalimumab to the treatment regimen of patients experiencing acute and severe sciatica resulted in a small decrease in leg pain and in significantly fewer surgical procedures.

     

A randomized,sham‐controlled,proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia

Objective

Recent evidence suggests that fibromyalgia is a disorder characterized by dysfunctional brain activity. Because transcranial direct current stimulation (tDCS) can modulate brain activity noninvasively and can decrease pain in patients with refractory central pain, we hypothesized that tDCS treatment would result in pain relief in patients with fibromyalgia.

Methods

Thirty‐two patients were randomized to receive sham stimulation or real tDCS with the anode centered over the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC) (2 mA for 20 minutes on 5 consecutive days). A blinded evaluator rated the patient's pain, using the visual analog scale for pain, the clinician's global impression, the patient's global assessment, and the number of tender points. Other symptoms of fibromyalgia were evaluated using the Fibromyalgia Impact Questionnaire and the Short Form 36 Health Survey. Safety was assessed with a battery of neuropsychological tests. To assess potential confounders, we measured mood and anxiety changes throughout the trial.

Results

Anodal tDCS of the primary motor cortex induced significantly greater pain improvement compared with sham stimulation and stimulation of the DLPFC (P < 0.0001). Although this effect decreased after treatment ended, it was still significant after 3 weeks of followup (P = 0.004). A small positive impact on quality of life was observed among patients who received anodal M1 stimulation. This treatment was associated with a few mild adverse events, but the frequency of these events in the active‐treatment groups was similar to that in the sham group. Cognitive changes were similar in all 3 treatment groups.

Conclusion

Our findings provide initial evidence of a beneficial effect of tDCS in fibromyalgia, thus encouraging further trials.

     

The relationship between self‐report and performance‐related measures: Questioning the content validity of timed tests

Objective

To examine the determinants of the modest correlation between self‐report and performance‐related measures in patients with osteoarthritis of the hip or knee.

Methods

Measures included the Lower Extremity Functional Scale (LEFS), the self paced walk, timed up‐and‐go, and stair test. Each performance measure consisted of 3 domains: time, pain (visual analog scale), and exertion (Borg scale). Activity specificity was assessed by examining correlations between the LEFS with single activity and multiple activity time scores. Domain specificity was examined by comparing correlations between the LEFS and single and multiple domain scores. The impact of measurement error was considered.

Results

Increasing the number of activity time scores had no effect. Forming a composite performance score based on time, pain, and exertion substantially increased the correlation from 0.44 (composite timed score) to 0.59 (pooled domain and activity score) (P = 0.009).

Conclusion

Performance scores based on time alone appear to inadequately represent the breadth of health concepts associated with functional status.

     

Dehydroepiandrosterone treatment of women with mild‐to‐moderate systemic lupus erythematosus: A multicenter randomized,double‐blind,placebo‐controlled trial

Objective

To evaluate the efficacy and tolerability of dehydroepiandrosterone (DHEA) at a dosage of 200 mg/day in adult women with active systemic lupus erythematosus (SLE).

Methods

In a multicenter randomized, double‐blind, placebo‐controlled trial, 120 adult women with active SLE received oral DHEA (200 mg/day; n = 61) or placebo (n = 59) for 24 weeks. The primary end point was the mean change from baseline in the Systemic Lupus Activity Measure (SLAM) score at 24 weeks of therapy. Secondary end points included time to first flare, change in SLE Disease Activity Index (SLEDAI) score, and physician's and patient's global assessment scores at week 24.

Results

The two groups were well balanced for baseline characteristics. Mean reductions in SLAM scores from baseline were similar and were not statistically significantly different between treatment groups (DHEA −2.6 ± 3.4 versus placebo −2.0 ± 3.8, mean ± SD). The number of patients with flares was decreased by 16% in the DHEA group (18.3% of DHEA‐treated patients versus 33.9% of placebo‐treated patients; P = 0.044, based on time to first flare). The mean change in the patient's global assessment was statistically significant between the two groups (DHEA −5.5 versus placebo 5.4; P = 0.005). The number of patients with serious adverse events, most of which were related to SLE flare, was significantly lower in DHEA‐treated patients compared with placebo‐treated patients (P = 0.010). Expected hormonal effects, including increased testosterone levels and increased incidence of acne, were observed. No life‐threatening reactions or serious safety issues were identified during this study.

Conclusion

The overall results confirm that DHEA treatment was well‐tolerated, significantly reduced the number of SLE flares, and improved patient's global assessment of disease activity.

     

Performance of a generic health‐related quality of life measure in a clinic population with rheumatic disease

Objective

To assess the performance of a generic health‐related quality of life (HRQOL) measure in a rheumatology clinic population.

Methods

Participants (n = 619) with fibromyalgia, rheumatoid arthritis, or osteoarthritis receiving care from rheumatologists completed mailed questionnaires that included the Behavioral Risk Factor Surveillance System (BRFSS) HRQOL measure and condition‐specific measures assessing disability, pain, fatigue, and helplessness. The BRFSS assesses global health and number of days in the past 30 of poor physical or mental health or activity limitation. The overall sample was described, followed by comparison of adjusted scores on all HRQOL measures by diagnosis.

Results

Participants reported mild difficulty with activities of daily living, marked pain and fatigue, and moderate helplessness. Participants reported a mean of 8 or more days out of 30 of poor physical and mental health and activity limitations; more than 40% reported poor or fair health. Participants with fibromyalgia reported more ill health on condition‐specific measures and the BRFSS HRQOL measures than did participants with osteoarthritis or rheumatoid arthritis.

Conclusion

The BRFSS HRQOL measure is a brief, easily administered, generic health indicator that shows differences among rheumatic disease diagnoses.

     

Treatment of fibromyalgia with cyclobenzaprine: A meta‐analysis

Objective

To systematically review the effectiveness of cyclobenzaprine in the treatment of fibromyalgia.

Methods

Articles describing randomized, placebo‐controlled trials of cyclobenzaprine in people with fibromyalgia were obtained from Medline, EMBase, Psyclit, the Cochrane Library, and Federal Research in Progress Database. Unpublished literature and bibliographies were also reviewed. Outcomes, including global improvement, treatment effects on pain, fatigue, sleep, and tender points over time, were abstracted.

Results

Five randomized, placebo‐controlled trials were identified. The odds ratio for global improvement with therapy was 3.0 (95% confidence interval [95% CI] 1.6–5.6) with a pooled risk difference of 0.21 (95% CI 0.09–0.34), which calculates to 4.8 (95% CI 3.0–11) individuals needing treatment for 1 patient to experience symptom improvement. Pain improved early on, but there was no improvement in fatigue or tender points at any time.

Conclusion

Cyclobenzaprine‐treated patients were 3 times as likely to report overall improvement and to report moderate reductions in individual symptoms, particularly sleep.

     

Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: A randomized,double‐blind,placebo‐controlled clinical trial at a single center

Objective

To evaluate the symptomatic effects of highly purified chondroitin 4 and chondroitin 6 sulfate (CS) therapy in patients with osteoarthritis (OA) of the hand.

Methods

This investigator‐initiated, single‐center, randomized, double‐blind, placebo‐controlled clinical trial included 162 symptomatic patients with radiographic evidence of hand OA (American College of Rheumatology criteria). Inclusion criteria included patient's assessment of global spontaneous hand pain of at least 40 mm on a 0–100‐mm visual analog scale (VAS) and functional impairment of at least 6 (0–30 scale) on the Functional Index for Hand OA (FIHOA) in the most symptomatic hand. Patients received either 800 mg of CS (n = 80 patients) or placebo (n = 82 patients) once daily for 6 months and were analyzed in an intent‐to‐treat approach. The two primary outcomes were the change in the patient's assessment of global spontaneous hand pain and in hand function (by FIHOA score) from baseline to month 6. Secondary outcomes were improvement in grip strength, duration of morning stiffness, acetaminophen consumption, and the investigator's global impression of treatment efficacy.

Results

There was a significantly more pronounced decrease in the patient's global assessment of hand pain in the CS group than in the placebo group (difference VAS scores −8.7 mm; P = 0.016). Hand function improved significantly more in the CS group than in the placebo group (difference in FIHOA scores −2.14; P = 0.008). There was a statistically significant between‐group difference in favor of CS for the duration of morning stiffness and for the investigator's global impression of treatment efficacy. Changes in grip strength, acetaminophen consumption, and safety end points were not significantly different between the two groups.

Conclusion

This study demonstrates that CS improves hand pain and function in patients with symptomatic OA of the hand and shows a good safety profile.

     

The Fibromyalgia Family Study: A Genome‐Wide Linkage Scan Study

Objective

Familial aggregation of fibromyalgia has been increasingly recognized. The goal of this study was to conduct a genome‐wide linkage scan to identify susceptibility loci for fibromyalgia.

Methods

We genotyped members of 116 families from the Fibromyalgia Family Study and performed a model‐free genome‐wide linkage analysis of fibromyalgia with 341 microsatellite markers, using the Haseman‐Elston regression approach.

Results

The estimated sibling recurrence risk ratio (λ_s) for fibromyalgia was 13.6 (95% confidence interval 10.0–18.5), based on a reported population prevalence of 2%. Genome‐wide suggestive evidence of linkage was observed at markers D17S2196 (empirical P [P_e] = 0.00030) and D17S1294 (P_e = 0.00035) on chromosome 17p11.2–q11.2.

Conclusion

The estimated sibling recurrence risk ratio (λ_s) observed in this study suggests a strong genetic component of fibromyalgia. This is the first report of genome‐wide suggestive linkage of fibromyalgia to the chromosome 17p11.2–q11.2 region. Further investigation of these multicase families from the Fibromyalgia Family Study is warranted to identify potential causal risk variants for fibromyalgia.

     

Sodium oxybate relieves pain and improves function in fibromyalgia syndrome: A randomized,double‐blind,placebo‐controlled,multicenter clinical trial

Objective

To evaluate the safety and efficacy of sodium oxybate for management of the symptoms of fibromyalgia syndrome (FMS).

Methods

Patients with FMS (according to the American College of Rheumatology 1990 criteria) were randomized, after discontinuing their prestudy medications for FMS, to receive 4.5 gm or 6 gm of sodium oxybate or matching placebo once per night for 8 weeks. The primary outcome variable (POV) was a composite score for changes from baseline in 3 coprimary self‐report measures: patient's pain rating (in daily electronic diaries) on a visual analog scale (PVAS), the Fibromyalgia Impact Questionnaire (FIQ) score, and the Patient Global Impression of Change (PGI‐C). A beneficial response rate for the POV composite score was defined as ≥20% improvement in the PVAS and FIQ scores plus a rating of “much better” or “very much better” on the PGI‐C. Secondary measures included subjective sleep outcomes (on the Jenkins Scale for Sleep) and quality‐of‐life measures. The analyses were based on an intent‐to‐treat (ITT) population.

Results

The ITT population included 188 patients with FMS, 78% of whom completed the trial. Significant benefit was observed with both dosages of sodium oxybate, according to changes in the POV and subjective sleep quality. Improvements in the PVAS score were significantly correlated with sleep outcomes. Sodium oxybate was well tolerated overall; dose‐related nausea (≤28% of patients) and dizziness (≤18% of patients) tended to resolve with continued therapy.

Conclusion

Sodium oxybate therapy was well tolerated and significantly improved the symptoms of FMS. Further study of sodium oxybate as a novel therapeutic option for FMS is warranted.

     

Canakinumab for the treatment of acute flares in difficult‐to‐treat gouty arthritis: Results of a multicenter,phase II,dose‐ranging study

Objective

To assess the efficacy and tolerability of canakinumab, a fully human anti–interleukin‐1β monoclonal antibody, for the treatment of acute gouty arthritis.

Methods

In this 8‐week, single‐blind, double‐dummy, dose‐ranging study, patients with acute gouty arthritis whose disease was refractory to or who had contraindications to nonsteroidal antiinflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg; n = 143) or an intramuscular dose of triamcinolone acetonide (40 mg; n = 57). Patients assessed pain using a 100‐mm visual analog scale.

Results

Seventy‐two hours after treatment, a statistically significant dose response was observed for canakinumab. All canakinumab doses were associated with numerically less pain than triamcinolone acetonide; thus, a dose with equivalent efficacy to triamcinolone acetonide 72 hours after treatment could not be determined. The reduction from baseline in pain intensity with canakinumab 150 mg was greater than with triamcinolone acetonide 24, 48, and 72 hours after treatment (differences of −11.5 mm [P = 0.04], −18.2 mm [P = 0.002], and −19.2 mm [P < 0.001], respectively), and 4, 5, and 7 days after treatment (all P < 0.05). Canakinumab significantly reduced the risk of recurrent flares versus triamcinolone acetonide (P ≤ 0.01 for all doses) (relative risk reduction 94% for canakinumab 150 mg versus triamcinolone acetonide). The overall incidence of adverse events was similar for canakinumab (41%) and triamcinolone acetonide (42%); most were mild or moderate in severity.

Conclusion

Our findings indicate that canakinumab 150 mg provides rapid and sustained pain relief in patients with acute gouty arthritis, and significantly reduces the risk of recurrent flares compared with triamcinolone acetonide.

     

Cognitive behavioral therapy for the treatment of juvenile fibromyalgia: A multisite,single‐blind,randomized, controlled clinical trial

Objective

Juvenile fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder in children and adolescents for which there are no evidence‐based treatments. The objective of this multisite, single‐blind, randomized clinical trial was to test whether cognitive–behavioral therapy (CBT) was superior to fibromyalgia (FM) education in reducing functional disability, pain, and symptoms of depression in juvenile FMS.

Methods

Participants were 114 adolescents (ages 11–18 years) with juvenile FMS. After receiving stable medications for 8 weeks, patients were randomized to either CBT or FM education and received 8 weekly individual sessions with a therapist and 2 booster sessions. Assessments were conducted at baseline, immediately following the 8‐week treatment phase, and at 6‐month followup.

Results

The majority of patients (87.7%) completed the trial per protocol. Intent‐to‐treat analyses showed that patients in both groups had significant reductions in functional disability, pain, and symptoms of depression at the end of the study, and CBT was significantly superior to FM education in reducing the primary outcome of functional disability (mean baseline to end‐of‐treatment difference between groups 5.39 [95% confidence interval 1.57, 9.22]). Reduction in symptoms of depression was clinically significant for both groups, with mean scores in the range of normal/nondepressed by the end of the study. Reduction in pain was not clinically significant for either group (<30% decrease in pain). There were no study‐related adverse events.

Conclusion

In this controlled trial, CBT was found to be a safe and effective treatment for reducing functional disability and symptoms of depression in adolescents with juvenile FMS.