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Biomedical subjects

T J Schnitzer

Publications and source records attributed to T J Schnitzer.

At least 19 recordsLinked to original sources
PubMed2004

The patient with a fragility fracture: an evolving role for the orthopaedic surgeon.

Osteoporosis can now be diagnosed readily, and treatments that increase bone mineral density and decrease fracture risk, even after fragility fracture has occurred, are now available. Clinical guidelines for management of osteoporosis unanimously recognize that fracture risk is highest among those who have already sustained a fracture, and encourage prompt evaluation and treatment of these individuals. Despite these guidelines, most women who experience fragility fractures remain untreated (for osteoporosis) by any of the physicians involved in their care. Barriers to diagnosis and treatment have been identified, including uncertainty about the responsibility for such management. The orthopaedic surgeon has a unique opportunity to initiate definitive osteoporosis evaluation and treatment in patients who present with fractures, and recent guidelines support the evolution of the role of the orthopaedist in this direction.

Female↗
PubMed2003

Response relationship of VAS and Likert scales in osteoarthritis efficacy measurement.

OBJECTIVE/BACKGROUND: Efficacy in osteoarthritis (OA) is principally measured using subjective visual analogue (VAS) and/or Likert scale responses. The relationship between these two scales and their relative precision in discriminating active from placebo treatment in OA patients was determined. DESIGN/METHODS: Patient overall pain assessment, and patient and investigator global assessments were each measured on a 100mm VAS and on a 0 to 4 point Likert scale in a 6-week OA study of rofecoxib vs placebo. The relationship between the VAS and Likert responses was examined graphically and via summary statistics. Analysis of variance was used to assess consistency of the VAS/Likert relationship over time and across the different endpoints. Precision was compared using effect size, and normality of VAS scale of measurement was assessed using the Shapiro-Wilk test. RESULTS: Mean VAS scores and changes from baseline at individual time points were generally highly correlated with corresponding Likert responses (r-values generally approximately 0.7-0.8). The magnitude of VAS values and changes varied depending on endpoint, on the associated magnitude of increment of Likert score, and on the Likert baseline value (i.e., where on the Likert scale the change was occurring). Precision of VAS and Likert responses to detect difference between treatments was generally similar with effect sizes approximately 1. Normality and homogeneity of variance of VAS scores was most closely approximated by actual changes in comparison to percent change or log-transformed measures. CONCLUSIONS: VAS and Likert responses are highly correlated and yield similar precision for discriminating treatments in OA patients. Since Likert responses are easier to administer and interpret, they may be preferable to measure OA response.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Two-year results of once-weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis.

The aim of this study was to provide confirmation that once-weekly dosing with 70 mg of alendronate (seven times the daily oral dose) and twice-weekly dosing with 35 mg is equivalent to the 10-mg once-daily regimen and to gain more extensive safety experience with this new dosing regimen. Twelve hundred fifty-eight postmenopausal women (aged 42-95 years) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak young adult mean or prior vertebral or hip fracture) were assigned to receive oral once-weekly alendronate, 70 mg (n = 519); twice-weekly alendronate, 35 mg (n = 369); or daily alendronate 10 mg (n = 370) for a total of 2 years of double-blind experience. Mean BMD increases from baseline (95% CI) at 24 months in the once-weekly, twice-weekly, and daily treatment groups, respectively, were 6.8% (6.4, 7.3), 7.0% (6.6,7.5), and 7.4% (6.9,7.8) at the lumbar spine and 4.1% (3.8,4.5), 4.3% (3.9,4.7), and 4.3% (3.9,4.7) at the total hip. These increases in BMD as well as the BMD increases at the femoral neck, trochanter, and total body and the reductions of biochemical markers of bone resorption (urinary cross-linked N-telopeptides of type I collagen [NTx]) and bone formation (serum bone-specific alkaline phosphatase [BSAP]) were similar for the three dosing regimens. All treatment regimens were well tolerated with a similar incidence of upper gastrointestinal (GI) adverse experiences. The incidence rates of clinical fractures, captured as adverse experiences, were similar among the groups. The 2-year results confirm the conclusion reached after 1 year that once-weekly alendronate is therapeutically equivalent to daily dosing, providing patients with a more convenient dosing option that may potentially enhance adherence to therapy.

Adult↗
PubMed2001

Cyclooxygenase-2--specific inhibitors: are they safe?

The basic tenet of the cyclooxygenase-2 (COX-2) hypothesis rests on the fact that sparing of inhibition of COX-1 should result in greater safety than if both COX isoforms are inhibited. This increase in safety should be most evident in those organs and tissues in which COX-1 alone has important, necessary physiologic functions (e.g., the stomach and platelets). Data from large clinical trials are now available to support the superior gastrointestinal safety of COX-2 inhibitors, not only for endoscopic endpoints but also for clinically significant outcomes. Additionally, lack of effect on platelets has been demonstrated at doses many times higher than being used clinically. Unfortunately, the COX-2 inhibitors still retain some of the side effects seen with traditional dual COX inhibitors (nonsteroidal anti-inflammatory drugs), namely, effects on the kidney that may manifest as an increased incidence of hypertension, edema, and associated clinical states. Similarly, effects on reproductive functions, endothelial function, and wound healing are theoretically possible but need to be evaluated in well-controlled clinical trials.

Animals↗
PubMed2001

Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial.

OBJECTIVE: To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. METHODS: This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. RESULTS: The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. CONCLUSION: Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years.

Adult↗
PubMed2001

A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee.

OBJECTIVE: To perform a randomized, double-blind, crossover clinical trial of diclofenac + misoprostol versus acetaminophen in ambulatory patients with osteoarthritis of the hip or knee. METHODS: Patients in 12 ambulatory care settings were eligible if they were age >40 years and if they had Kellgren/Lawrence radiographic grade 2-4 osteoarthritis of the knee or hip and a score of > or =30 mm on a 100-mm visual analog pain scale. Patients were randomized to one of two groups, 75 mg diclofenac + 200 microg misoprostol twice daily or 1,000 mg acetaminophen 4 times daily (each for 6 weeks), and were then crossed over to the other treatment for 6 weeks. A placebo was included in each treatment regimen to enable double blinding. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index and the visual analog pain scale of the Multidimensional Health Assessment Questionnaire. Safety was assessed using a standard form to review adverse events. RESULTS: We enrolled 227 patients, of whom 218 provided data for the first treatment period and 181 provided data for both treatment periods. Significantly higher levels of improvement in the primary outcomes were seen for diclofenac + misoprostol than for acetaminophen (P < 0.001). Adverse events were more common when patients took diclofenac + misoprostol (P = 0.046). Diclofenac + misoprostol was rated as "better" or "much better" by 57% of the 174 patients who provided such ratings for both treatment periods, while acetaminophen was rated as "better" or "much better" by 20% of these patients, and 22% reported no difference (P < 0.001). Differences favoring diclofenac + misoprostol over acetaminophen were greater in patients with more severe osteoarthritis according to baseline pain scores, radiographs, or number of involved joints. CONCLUSION: Patients with osteoarthritis of the hip or knee had significantly greater improvements in pain scores over 6 weeks with diclofenac + misoprostol than with acetaminophen, although patients with mild osteoarthritis had similar improvements with both drugs. Acetaminophen was associated with fewer adverse events.

Acetaminophen↗
PubMed2001

Osteoarthritis management: the role of cyclooxygenase-2-selective inhibitors.

BACKGROUND: Cyclooxygenase (COX)-2-selective inhibitors are a new type of nonsteroidal anti-inflammatory drug (NSAID) for the management of pain caused by osteoarthritis (OA). The most recent OA guidelines from the American College of Rheumatology were published in 2000 because new therapies such as the COX-2-selective inhibitors had been introduced for the management of OA. OBJECTIVE: Because more data are now available on efficacy and safety issues with COX-2-selective inhibitors, NSAIDs, and acetaminophen, this review focuses on how COX-2-selective inhibitors may change the pharmacologic management of patients with OA. METHODS: References were obtained from MEDLINE, BIOSIS, EMBASE, and Internet searches of the literature. CONCLUSIONS: The safety and efficacy of two COX-2-selective inhibitors, rofecoxib and celecoxib, have been examined in a number of clinical trials, and these agents have been shown to offer efficacy similar to that of NSAIDs. Acetaminophen continues to be the initial drug of choice for the management of OA because of its efficacy, safety, cost, and availability. COX-2-selective inhibitors should be considered in patients with OA who do not respond to or cannot tolerate therapy with acetaminophen. COX-2-selective inhibitors have an improved gastrointestinal (GI) safety profile compared with traditional NSAIDs and should be chosen over NSAIDs if prescription plan access and/or expense is not a concern. COX-2-selective inhibitors are clinically indicated for patients at increased risk of developing NSAID-induced GI complications, a population in whom the use of COX-2-selective inhibitors may be cost-effective because the incidence and mortality associated with serious GI adverse events and use of expensive GI comedications would be reduced.

Acetaminophen↗
PubMed2001

Use of nonsteroidal anti-inflammatory drugs and gastroprotective agents before the advent of cyclooxygenase-2-selective inhibitors: analysis of a large United States claims database.

BACKGROUND: Previous studies have shown that 20% to 40% of patients requiring nonsteroidal anti-inflammatory drugs (NSAIDs) are concomitantly prescribed gastroprotective agents (GPAs) such as proton pump inhibitors (PPIs) and H2-receptor antagonists. OBJECTIVE: The purpose of this study was to examine NSAID prescription patterns and the concurrent use of GPAs in a large national sample of patients who were prescribed NSAIDs for the first time. METHODS: Patterns of NSAID use, particularly chronic NSAID use, and of concomitant use of GPAs were examined using a large US-based prescription database. Patients with at least 1 NSAID prescription dispensed between May 1 and August 31, 1998, were identified. Persons with any NSAID prescription within 4 months prior to the first (index) prescription were excluded. The remaining patients were defined as new NSAID users and then classified as chronic users (> or = 30 days of supply of NSAIDs during the 120 days of follow-up after the first NSAID prescription) or acute users (<30 days of NSAID supply during the 120 days of follow-up). Concomitant GPA use was defined as receipt of any GPA prescription between the fill date of NSAID prescription and 125% of days of supply. NSAIDs included diclofenac/misoprostol (in a fixed combination), diclofenac, naproxen, nabumetone, ibuprofen, and "other" (comprising several less frequently prescribed agents). Patients were classified as users of a particular NSAID based on the first NSAID prescription they received. GPAs included PPIs, H2-receptor antagonists, and misoprostol. RESULTS: A total of 3,028,808 new NSAID users were identified. Chronic NSAID users (47.8% of the sample) were older than acute users. The percentage of new chronic users aged > or = 65 years for each of the NSAIDs was 41.2% for diclofenac/ misoprostol, 33.0% for nabumetone, 30.8% for diclofenac, 20.4% for naproxen, and 20.3% for ibuprofen. The percentage of women was higher among patients treated with diclofenac/misoprostol than among patients treated with all other NSAIDs (P < 0.001). During the 120 days of follow-up, the percentages of NSAID users with concomitant GPA use were 22.7% for diclofenac/misoprostol, 16.3% for diclofenac, 11.5% for naproxen, 18.0% for nabumetone, 12.3% for ibuprofen, and 14.8% for other NSAIDs. Based on days of supply, the rates of concomitant GPA use were 31.1%, 23.6%, 17.6%, 27.3%, 18.8%, and 22.5% for diclofenac/misoprostol, diclofenac, naproxen, nabumetone, ibuprofen, and other NSAID users, respectively. Among those who were taking GPAs before the NSAID index prescription date, -89% continued GPA therapy. CONCLUSIONS: Approximately 22% of the days of NSAID supply were covered by GPAs. Prior GPA use was the strongest predictor of subsequent concomitant GPA/ NSAID use. Differences in GPA use were observed among patients using different NSAIDs.

Adolescent↗
PubMed2001

Cox-2 inhibitors and other nonsteroidal anti-inflammatory drugs in the treatment of pain in the elderly.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed therapies for acute and chronic pain in the elderly. NSAIDs are effective in treating many disorders, but their use often is limited by toxicities, especially gastrointestinal and renal toxicity. COX-2 inhibitors are a major therapeutic advance, providing the analgesic and anti-inflammatory activity of NSAIDs, with a significant improvement in gastrointestinal safety. These new agents may be ideal therapies for older patients at risk for NSAID-related gastrointestinal toxicity.

Aged↗
PubMed2001

Update on alendronate for osteoporosis: once-weekly dosing.

Alendronate (Fosamax, Merck & Co.) is now available in a 70 mg formulation to be taken once a week for osteoporosis. Earlier studies demonstrated that alendronate is highly effective for increasing bone density, reducing bone turnover rate and reducing the risk of fractures. A subsequent clinical trial reported that the once-weekly dosing regimen is therapeutically equivalent to the daily regimen. Administering alendronate (70 mg) once a week effectively provides continuous inhibition of bone resorption because bone resorption by osteoclasts is a slow process that typically requires 2-3 weeks for completion and alendronate remains at active bone remodelling sites for a sustained period and (when present in sufficient concentration) effectively inhibits bone resorption. Bisphosphonates are currently the pre-eminent therapy for osteoporosis. Once-weekly alendronate represents a major advance in convenience because oral bisphosphonates must be taken in the fasting state with water at least 30 minutes before consuming food or beverages. Sales data several months after introduction of once-weekly alendronate into the marketplace demonstrate rapid and extensive acceptance of this new regimen.

Alendronate↗
PubMed2001

Precision of composite measures of osteoarthritis efficacy in comparison to that of individual endpoints.

OBJECTIVE: Osteoarthritis (OA) clinical studies generally employ various endpoints to evaluate a spectrum of disease manifestations. Compared with individual endpoints, a composite measure might (1) provide a uniform outcome measure of OA efficacy with greater face validity, (2) address multiplicity, and (3) enhance precision. Combinations of endpoints were analyzed to investigate precision of composite measures of OA efficacy. METHODS: We reanalyzed three 6 week, placebo controlled, double blind, parallel group studies (2 by the same protocol) of the cyclooxygenase-2 (COX-2) specific inhibitor rofecoxib. The average change from baseline at study weeks 2, 4, and 6 was assessed for 10 individual response variables, including patient and investigator global assessments, WOMAC 3.0V OA Index pain, stiffness and physical function subscales, graded study joint tenderness, and rescue analgesic use. Relationships among variables were evaluated using pairwise correlations and principal components analysis. The precision of variables to differentiate rofecoxib from placebo was evaluated using effect size (i.e., mean difference between rofecoxib versus placebo divided by pooled SD). RESULTS: Correlations among all pairs of response variables ranged from 0.5 to 0.9, except those with tenderness (0.4 to 0.6) and those with analgesic use (0.2 to 0.4). The first principal component explained about 70% of the total variability, with weights generally similar (0.17 for rescue analgesic use, 0.25 for tenderness, and 0.30 to 0.37 for the others). These results indicate that nearly all measures are closely related. Based on these results, various linear combinations of the 9 endpoints were formed and their precision to discriminate active treatment from placebo was compared to that of the individual endpoints. Effect sizes of the individual endpoints ranged from 0.6 to 1.1; those of the composites from 0.7 to 0.9. The results were very consistent between study protocols. CONCLUSION: In comparison to individual endpoints, composite analyses of OA clinical endpoints do not increase precision to discriminate active treatment from placebo.

Analgesics↗
PubMed2000

Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group.

BACKGROUND: Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis. METHODS: We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers). RESULTS: Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups. CONCLUSIONS: In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.

Adult↗
PubMed2000

Quantification of progressive joint space narrowing in osteoarthritis of the hip: longitudinal analysis of the contralateral hip after total hip arthroplasty.

OBJECTIVE: The rate of progressive joint space narrowing in the contralateral hip after total hip arthroplasty (THA) for osteoarthritis (OA) and the factors which may predispose patients to more aggressive joint space narrowing remain undefined. The current study sought to evaluate the rate and pattern of, and risk factors for, progressive joint space narrowing in the contralateral hip after THA for OA. METHODS: Each patient who underwent THA for OA in 1984-1985 was followed up longitudinally, and annual anteroposterior (AP) pelvis radiographs were obtained. The radiographic joint space width (JSW) of each contralateral hip joint was quantified, and the rates of JSW narrowing were determined. Evaluation of potential risk factors for accelerated progression of joint space narrowing included age, sex, side of surgery, weight, height, body mass index (BMI), hip pain, etiology of OA, and Kellgren/Lawrence radiographic grade. RESULTS: Ninety-nine patients and 619 AP pelvis radiographs were evaluated. The median initial JSW was 3.48 mm (interquartile range 1.55). JSW declined in a linear manner at a median rate of 0.10 mm/year. The rate of decline between baseline and followup in 20 months was predictive of the overall slope. Two subpopulations were identified. Eighty-five percent of patients maintained a slow decline in JSW (< or =0.2 mm/year), and 15% exhibited an accelerated decline in JSW (>0.2 mm/year). Kellgren/ Lawrence radiographic grade > or =2 and a diagnosis of primary OA were each associated with a more rapid decline in JSW (P = 0.006 and P = 0.02, respectively). Initial JSW, age, sex, weight, height, BMI, and hip pain were not risk factors for rapid decline in JSW. CONCLUSION: Radiographic hip JSW may be reliably quantified and followed up longitudinally using standard AP radiographs. Progression of JSW narrowing in the contralateral hip after THA for OA proceeds in a linear manner over several years. A subpopulation of patients with accelerated narrowing of contralateral JSW may be identified within 20 months, and may represent a suitable population with which to assess the potential efficacy of new disease-modifying agents.

Adult↗
PubMed2000

Knee pain and joint loading in subjects with osteoarthritis of the knee.

Although treatments for osteoarthritis of the knee are often directed at relieving pain, pain may cause patients to alter how they perform activities to decrease the loads on the joints. The knee-adduction moment is a major determinant of the load distribution between the medial and lateral plateaus. Therefore, the interrelationship between pain and the external knee-adduction moment during walking may be especially important for understanding mechanical factors related to the progression of medial tibiofemoral osteoarthritis. Fifty-three subjects with symptomatic radiographic evidence of osteoarthritis of the knee were studied. These subjects were a subset of those enrolled in a double-blind study in which gait analysis and radiographic and clinical evaluations were performed after a 2-week washout of anti-inflammatory and analgesic treatment. The subjects then took a nonsteroidal anti-inflammatory drug, acetaminophen, or placebo for 2 weeks, and the gait and clinical evaluations were repeated. The change in the peak external adduction moment between the two evaluations was inversely correlated with the change in pain (R = 0.48, p < 0.001) and was significantly different between those whose pain increased (n = 7), decreased (n = 18), or remained unchanged (n = 28) (p = 0.009). Those with increased pain had a significant decrease in the peak external adduction (p = 0.005) and flexion moments (p = 0.023). In contrast, the subjects with decreased pain tended to have an increase in the peak external adduction moment (p = 0.095) and had a significant increase in the peak external extension moment (p = 0.017). The subjects whose pain was unchanged had no significant change in the peak external adduction (p = 0.757), flexion (p = 0.234), or extension (p = 0.465) moments. Thus, decreases in pain among patients with medial tibiofemoral osteoarthritis were related to increased loading of the degenerative portion of the joints. Additional long-term prospective studies are needed to determine whether increased loading during walking actually results in accelerated progression of the disease.

Aged↗
PubMed2000

Microemulsion formulation of cyclosporin (Sandimmun Neoral) vs Sandimmun: comparative safety, tolerability and efficacy in severe active rheumatoid arthritis. On behalf of the OLR 302 Study Group.

OBJECTIVE: To compare the safety, tolerability and efficacy of the new oral microemulsion formulation of cyclosporin A (CyA; Sandimmun Neoral) and the original CyA formulation (Sandimmun), in patients with severe active rheumatoid arthritis (RA), over a 12-month period. METHODS: In this double-blind, multicentre study, patients were randomized to treatment with Neoral or Sandimmun, starting with 2.5 mg/kg/day, with dose adjustments after 4 weeks. Primary efficacy criteria included patients' assessment of disease activity. Pharmacokinetic and safety assessments were performed at regular intervals. RESULTS: Compared with Sandimmun, Neoral showed a consistent trend towards greater clinical efficacy from week 12 onwards, including a significant difference in patients' assessment of disease activity at the study end-points. A significantly lower increase in dose from baseline was observed with Neoral at week 24. Pharmacokinetic assessments at week 24 showed increased absorption and decreased variability with Neoral. No differences in safety were found between treatment groups. CONCLUSION: These observations indicate that Neoral is as safe and at least as effective as Sandimmun and have important implications for patient management given the increasing role for CyA in the treatment of severe, active RA.

Antirheumatic Agents↗
PubMed2000

Efficacy of tramadol in treatment of chronic low back pain.

OBJECTIVE: To evaluate the efficacy and safety of tramadol in the treatment of chronic low back pain. METHODS: A 3 phase trial: (1) a washout/screening phase; (2) a 3 week, open label, run-in phase; and (3) a 4 week, randomized, placebo controlled, double blind treatment phase. Three hundred eighty outpatients between 21 and 79 years with chronic low back pain with no or a distant history of back surgery enrolled in the open label phase and were treated with tramadol up to 400 mg/day. At the end of the open label phase, patients who tolerated tramadol and perceived benefit from it were randomized to continue treatment with tramadol or to convert to placebo in the double blind phase. Reasons for discontinuing from the open label phase included adverse events, 78 patients (20.5%); drug ineffective, 23 patients (6.1%); and other reasons, 25 patients (6.6%). Two hundred fifty-four patients entered the double blind phase, during which the daily dose was maintained within the range 200-400 mg tramadol or equivalent amount of placebo. The primary outcome measure in the double blind phase was the time to discontinuation due to inadequate pain relief. RESULTS: The distribution of time to therapeutic failure was significantly (p < or = 0.0001) different in the tramadol group compared to placebo. Kaplan-Meier estimate of the cumulative discontinuation rate due to therapeutic failure was 20.7% in the tramadol group and 51.3% in the placebo group. There were significantly lower (p < or = 0.0001) mean pain visual analog scores (10 cm scale) among tramadol patients (3.5 cm) compared to placebo patients (5.1 cm) at the final visit of the double blind phase. Tramadol patients scored significantly better on the McGill Pain Questionnaire (p = 0.0007) and the Roland Disability Questionnaire (p = 0.0001). Five of 127 tramadol treated patients and 6/127 placebo treated patients discontinued treatment during the double blind phase due to an adverse event. Commonly reported adverse events with tramadol included nausea, dizziness, somnolence, and headache. CONCLUSION: Among patients who tolerated it well, tramadol was effective for the treatment of chronic low back pain.

Adult↗
PubMed1999

Tramadol allows reduction of naproxen dose among patients with naproxen-responsive osteoarthritis pain: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To demonstrate that in patients receiving naproxen for the pain of osteoarthritis (OA), the addition of tramadol will allow a reduction in the naproxen dosage without compromising pain relief. METHODS: This trial consisted of a 5-week open-label run-in and an 8-week double-blind phase. Patients with at least moderate pain (> or =40 mm on a 100-mm visual analog scale) of OA of the knee after a 1-week medication washout were treated with naproxen 500 mg/day for 1 week. Patients whose pain scores were reduced to <20 mm were discontinued. The remaining patients received naproxen 1,000 mg/day for 3 weeks. Tramadol 200 mg/day was added during the third week. Patients were then randomized in a double-blind manner to continue tramadol 200 mg/day or to begin placebo in addition to naproxen. Randomization was stratified based on response to naproxen 1,000 mg/day. During the double-blind phase, the naproxen dose was reduced by 250 mg every 2 weeks. The primary efficacy end point was the minimum effective naproxen dose (MEND). The MEND was defined as 250 mg above the naproxen daily dosage at which pain relief was no longer adequate. Patients discontinuing the double-blind phase of the study for reasons other than lack of efficacy were assigned a MEND equal to the last naproxen dose received. If the effect of treatment between the responder and nonresponder groups was statistically different, the difference in the MEND was assessed separately within the groups. RESULTS: Of 236 patients randomized (mean age 61 years; 147 females), 90 were stratified as naproxen responders and 146 as naproxen nonresponders. There was a significant difference (P = 0.040) in the treatment effect between the naproxen responders and nonresponders, thus demonstrating a difference in the way responders and nonresponders react to a decrease in naproxen dosage after the addition of tramadol. Among naproxen responders, the MEND was significantly lower in patients receiving tramadol (n = 36) than in patients receiving placebo (n = 54), 221 mg versus 407 mg, respectively (P = 0.021). For the naproxen nonresponders, the mean MEND was 419 mg in the tramadol group and 396 mg in the placebo group (P = 0.706). CONCLUSION: In patients with painful OA of the knee responding to naproxen 1,000 mg/day, the addition of tramadol 200 mg/day allows a significant reduction in the dosage of naproxen without compromising pain relief.

Aged↗