[show abstract][hide abstract] ABSTRACT: Tumour necrosis factor alpha (TNFalpha) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). Treatment with TNFalpha inhibitors reduces disease activity and improves outcomes for patients with RA. This study evaluated the efficacy and safety of certolizumab pegol 400 mg, a novel, poly-(ethylene glycol) (PEG)ylated, Fc-free TNFalpha inhibitor, as monotherapy in patients with active RA.
In this 24-week, multicentre, randomised, double-blind, placebo-controlled study, 220 patients previously failing > or =1 disease-modifying antirheumatic drug (DMARD) were randomised 1:1 to receive subcutaneous certolizumab pegol 400 mg (n = 111) or placebo (n = 109) every 4 weeks. The primary endpoint was 20% improvement according to the American College of Rheumatology criteria (ACR20) at week 24. Secondary endpoints included ACR50/70 response, ACR component scores, 28-joint Disease Activity Score Erythrocyte Sedimentation Rate 3 (DAS28(ESR)3), patient-reported outcomes (including physical function, health-related quality of life (HRQoL), pain and fatigue) and safety.
At week 24, the ACR20 response rates were 45.5% for certolizumab pegol 400 mg every 4 weeks vs 9.3% for placebo (p<0.001). Differences for certolizumab pegol vs placebo in the ACR20 response were statistically significant as early as week 1 through to week 24 (p<0.001). Significant improvements in ACR50, ACR components, DAS28(ESR)3 and all patient-reported outcomes were also observed early with certolizumab pegol and were sustained throughout the study. Most adverse events were mild or moderate and no deaths or cases of tuberculosis were reported.
Treatment with certolizumab pegol 400 mg monotherapy every 4 weeks effectively reduced the signs and symptoms of active RA in patients previously failing > or =1 DMARD compared with placebo, and demonstrated an acceptable safety profile. Trial registration number: NCT00548834.
Annals of the rheumatic diseases 11/2008; 68(6):805-11. · 8.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Low back pain is an extremely common patient complaint. Most cases resolve fairly quickly after the acute episode. However, a small but significant number of patients develop chronic low back pain; a persistent disabling condition. Patients suffer from unremitting pain and often become functionally impaired. Multiple patient characteristics have been identified that place patients at risk for developing chronic low back pain. Currently, it is difficult to find clinical guidelines on how best to manage chronic low back pain, and it remains a substantial treatment challenge for both physicians and patients. The causes, risk factors, prognosis and treatment strategies for chronic low back pain will be discussed in this chapter. The evidence regarding different pharmacological and non-pharmacological treatment modalities will be reviewed and a logical, focused treatment strategy will be outlined.
Bailliè re s Best Practice and Research in Clinical Rheumatology 09/2006; 20(4):707-20. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Ankylosing spondylitis and rheumatoid arthritis are disorders that cause marked alterations in the structure and function of the axial skeleton. Ankylosing spondylitis causes calcification of spinal structures causing limited motion. Rheumatoid arthritis causes synovial hypertrophy, joint destruction, and spinal instability. Surgical therapy for patients with ankylosing spondylitis corrects angular deformities with spinal osteotomies, and stabilization for spinal fractures. Spinal operative therapy for rheumatoid arthritis concentrates on correction of abnormal motion in the cervical spine. Advances in the medical therapy of spondyloarthritis have resulted in control of the inflammation of the axial skeleton halting the damage to spinal structures. The new biologic therapies for ankylosing spondylitis prevent progression of disease. Similarly, these same biologic therapies can also control the progression of rheumatoid arthritis including the cervical spine. The new medical therapies are very effective in preventing joint damage. The need for surgical intervention for patients with ankylosing spondylitis and rheumatoid arthritis will become a rare event in the setting of the new medical therapies for these inflammatory arthropathies.
Clinical Orthopaedics and Related Research 03/2006; 443:208-21. · 2.79 Impact Factor
[show abstract][hide abstract] ABSTRACT: This prospective, randomized, open-label, multicenter, community-based study was conducted to compare cyclobenzaprine 5 mg three times daily (TID) orally (CYC5) given for 7 days as monotherapy or in combination with ibuprofen 400 mg TID (CYC5/IBU400) or 800 mg TID (CYC5/IBU800) in adults with acute neck or back pain with muscle spasm.
Eligible patients were 18-65 years old, had cervical or thoracolumbar pain and spasm for < or = 14 days, and, aside from the prescribed study medications, discontinued treatment with all analgesics, anti-inflammatory agents, and skeletal muscle relaxants during the study period. Randomization was 1:1:1 to the three treatment groups. Treatment outcome was assessed after 3 and 7 days of therapy using five patient-rated scales: spasm, pain, patient global impression of change (PGIC), medication helpfulness, and Oswestry Disability Index (ODI).
A total of 867 patients provided postbaseline data and were included in the intent-to-treat population (CYC5, n = 288; CYC5/IBU400, n = 286; CYC5/IBU800, n = 293). All three treatment groups demonstrated significant improvements from baseline in PGIC, spasm, pain, ODI, and medication helpfulness (p < 0.001 for all comparisons) after 3 and 7 days of therapy. There were no significant differences in mean PGIC among groups after 3 days of therapy (p = 0.65 for treatment effect) or after 7 days of therapy (primary endpoint; p = 0.41). A PGIC responder analysis of changes from baseline showed that 88% and 93% of patients reported at least mild improvement after 3 and 7 days of therapy, respectively. All three treatments were well tolerated, with no significant differences between treatments regarding the number of adverse events (AEs) reported or number of patients reporting AEs. The most common AEs in all groups were fatigue, somnolence, dizziness, sedation, and nausea. Limitations of this study include an unblinded design and possible introduction of bias into efficacy and safety results by use of a voluntary telephone reporting system.
This randomized, community-based clinical trial demonstrated that combination therapy with cyclobenzaprine 5 mg TID plus ibuprofen was not superior to cyclobenzaprine 5 mg TID alone in adult patients with acute neck and back pain with muscle spasm. All treatments were well tolerated.
Current Medical Research and Opinion 09/2005; 21(9):1485-93. · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: The lumbar spine is a common location for osteoarthritis. The axial skeleton demonstrates the same classic alterations of cartilage loss, joint instability, and osteophytosis characteristic of symptomatic disease in the appendages. Despite these similarities, questions remain regarding the lumbar spine facet joints as a source of chronic back pain. The facet joints undergo a progression of degeneration that may result in pain. The facet joints have sensory input from two spinal levels that makes localization of pain difficult. Radiographic studies describe intervertebral disc abnormalities in asymptomatic individuals that are associated with, but not synonymous for, osteoarthritis. Patients who do not have osteoarthritis of the facet joints on magnetic resonance scan do not have back pain. Single photon emission computed tomography scans of the axial skeleton are able to identify painful facet joints with increased activity that may be helped by local anesthetic injections. Low back pain is responsive to therapies that are effective for osteoarthritis in other locations. Osteoarthritis of the lumbar spine does cause low back pain.
Current Pain and Headache Reports 01/2005; 8(6):512-7. · 1.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Valdecoxib, a cyclooxygenase (COX)-2 specific inhibitor, is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and primary dysmenorrhea. Therapeutic doses of COX-2 specific inhibitors are as effective as nonspecific nonsteroidal anti-inflammatory drugs in reducing inflammatory pain while sparing the gastrointestinal and platelet toxicity associated with nonspecific COX-1 inhibition.
The aim of this study was to assess the analgesic efficacy and tolerability of valdecoxib 40 mg/d compared with placebo in the treatment of chronic low back pain.
This 4-week, prospective, randomized, double-blind placebo-controlled, parallel-group study was conducted at 37 centers across the United States and 5 centers in Canada. Patients aged > or =18 years with chronic low back pain in flare were enrolled. Patients were randomized to receive valdecoxib 40-mg/d or placebo tablets, once daily for 4 weeks. Patients rated low back pain intensity on a visual analog scale and completed the Roland-Morris Disability Questionnaire and the modified Brief Pain Inventory-Short Form (mBPI-SF) at each visit.
Two hundred ninety-three patients were enrolled. The valdecoxib group comprised 148 patients (81 women, 67 men; mean [SD] age, 48.6 [13.3] years; mean [SD] body weight, 86.6 [20.9] kg), and the placebo group included 145 patients (85 women, 60 men; mean [SD] age, 48.7 [12.6] years; mean [SD] body weight, 85.6 [19.9] kg). Of the enrolled patients, 249 completed the study: 134 patients (91%) who received valdecoxib and 115 patients (79%) who received placebo. No statistically significant differences in patient baseline characteristics were noted between treatment groups, except in response to 1 mBPI-SF question; patients in the valdecoxib group reported significantly greater interference in relations with other people due to pain than did those in the placebo group (P = 0.048). Changes from baseline in low back pain intensity were significantly greater in valdecoxib-treated patients at each assessment (all, P < 0.001 vs placebo). Pain scores on the mBPI-SF indicated significantly greater pain relief with valdecoxib at each assessment (all, P < or = 0.014 vs placebo). Improvements in mean Roland-Morris Disability Questionnaire score with valdecoxib were significantly greater than with placebo at each assessment (all, P < or = 0.003). Although the overall incidence of adverse events (AEs) was significantly higher among patients receiving valdecoxib than those receiving placebo (35.1% vs 24.1%, respectively; P = 0.042), no significant differences were found between groups for the incidence of any individual AE. Most AEs (89% [77/87 total events]) were mild or moderate in severity.
In this study of patients with chronic low back pain, valdecoxib 40 mg/d provided rapid relief (within 1 week) and consistent relief (over 4 weeks). In addition, significant improvement in function and decreased disability were found with valdecoxib compared with placebo.
[show abstract][hide abstract] ABSTRACT: Cyclobenzaprine hydrochloride is a muscle relaxant that is effective in improving muscle spasm, reducing local pain and tenderness, and increasing range of motion in acute, painful musculoskeletal conditions. Sedation is the most common adverse event associated with its use at the usual dosage of 10 mg TID. Studies in healthy adults suggest that a lower dose may produce less sedation. Because cyclobenzaprine's duration of action is 4 to 6 hours, reducing the dosing frequency to 10 mg BID would create a potentially painful untreated interval between doses. The alternative is administration of a lower dose (eg, 5 or 2.5 mg) TID.
These studies were designed to assess the efficacy and tolerability of cyclobenzaprine 2.5, 5, and 10 mg TID compared with placebo in patients with acute musculoskeletal spasm.
In 2 randomized, double-blind, placebo-controlled, parallel-group trials conducted at primary care centers in the United States, adult patients with acute painful muscle spasm of the lumbar or cervical region were randomly assigned to receive treatment with 2.5, 5, or 10 mg cyclobenzaprine TID or placebo for 7 days (study 1: cyclobenzaprine 5 or 10 mg TID or placebo; study 2: cyclobenzaprine 2.5 or 5 mg TID or placebo). The primary efficacy measures were patient-rated clinical global impression of change, medication helpfulness, and relief from starting backache. Neither study included a nonsteroidal anti-inflammatory drug (NSAID) as an active control. Although physicians frequently prescribe an analgesic or NSAID in addition to cyclobenzaprine, these studies were not designed to assess whether adding cyclobenzaprine provides a benefit over that of an analgesic.
One thousand four hundred five patients (737 study 1; 668 study 2), two thirds with low back pain and one third with neck pain, were randomized to treatment. Their mean age was 42 years, and approximately 89% were white. In both studies, patients receiving cyclobenzaprine 5 or 10 mg had significantly higher mean scores on the primary efficacy measures compared with those receiving placebo (study 1-P</=0.001 cyclobenzaprine 5 and 10 mg vs placebo, all measures at visits 2 and 3; study 2-P</=0.03 cyclobenzaprine 2.5 mg vs placebo, relief from starting backache on day 3 only; cyclobenzaprine 5 mg vs placebo, patient-rated clinical global impression of change, medication helpfulness, and relief from starting backache at visit 3 or day 7 only). On day 7, significantly more patients receiving cyclobenzaprine 5 or 10 mg reported relief compared with placebo recipients (P < 0.05 all cyclobenzaprine groups vs placebo). Onset of relief was apparent within 3 or 4 doses of the 5-mg regimen. In the subanalysis of the proportion of responders in the pooled 5-mg groups who did and did not report somnolence, a meaningful treatment effect was observed on all primary efficacy variables in patients who did not report somnolence, suggesting that efficacy was independent of sedation. Cyclobenzaprine was well tolerated. Somnolence and dry mouth, the most common adverse effects, were mild and dose related. Overall, >/= 1 adverse event was reported in 54.1%, 61.8%, and 35.4% of patients receiving cyclobenzaprine 5 or 10 mg or placebo, respectively, in study 1 and by 43.9%, 55.9%, and 35.4% of patients receiving cyclobenzaprine 2.5 or 5 mg or placebo, respectively, in study 2. Adverse events were the primary reason for discontinuation of treatment in the cyclobenzaprine 5- and 10-mg groups in both studies. In study 2, ineffectiveness of therapy was the main reason for discontinuation of therapy in the group receiving cyclobenzaprine 2.5 mg.
Cyclobenzaprine 2.5 mg TID was not significantly more effective than placebo. The cyclobenzaprine 5- and 10-mg TID regimens were associated with significantly higher mean efficacy scores compared with placebo. Cyclobenzaprine 5 mg TID was as effective as 10 mg TID, and was associated with a lower incidence of sedation.
[show abstract][hide abstract] ABSTRACT: The selection of appropriate therapy for the management of musculoskeletal pain requires understanding the general principles of pain management and recognizing the importance of using both nonpharmacologic and pharmacologic modalities. Aspects to consider include the type of pain, its intensity and duration, presence of comorbidities and/or use of concomitant medications, patient age, likelihood of adverse effects, psychosocial factors, past pain treatments, patient preferences, and costs.
Postgraduate Medicine 08/2002; 112(1 Suppl):8-12. · 1.97 Impact Factor