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Biomedical subjects

T J Schnitzer

Publications and source records attributed to T J Schnitzer.

At least 37 records · Page 2Linked to original sources
PubMed1999

The safety profile, tolerability, and effective dose range of rofecoxib in the treatment of rheumatoid arthritis. Phase II Rofecoxib Rheumatoid Arthritis Study Group.

Nonsteroidal anti-inflammatory drugs. (NSAIDs) inhibit both cyclooxygenase (COX)-1 and COX-2 isoenzymes and are effective in the treatment of inflammatory disorders. This 8-week, double-masked, placebo-controlled trial was undertaken to assess the safety profile, tolerability, and effective dose range of once-daily rofecoxib, a COX-2-specific inhibitor, in the treatment of rheumatoid arthritis (RA). After a 3- to 15-day washout of prior NSAID therapy, 658 patients were randomly allocated to receive placebo or rofecoxib 5 mg, 25 mg, or 50 mg once daily. Safety profile, tolerability, and efficacy were evaluated after 2, 4, and 8 weeks of therapy. Six hundred fifty-eight patients (168, 158, 171, and 161 in the placebo and 5-mg, 25-mg, and 50-mg rofecoxib groups, respectively) were enrolled at 79 clinical centers in the United States. Mean age was 55 years, mean duration of RA was 10 years, and 506 (77%) of the 658 patients were female. All groups had similar baseline demographic characteristics. Patients taking rofecoxib 25 and 50 mg showed significant clinical improvement compared with those taking placebo; 43.9% in the rofecoxib 25-mg group and 49.7% in the rofecoxib 50-mg group completed the treatment period and achieved an American College of Rheumatology 20 response (P = 0.025 and 0.001 vs. placebo, respectively). The 5-mg dose of rofecoxib did not differ significantly from placebo. Patients in the rofecoxib 25- and 50-mg groups showed significant improvement in key individual efficacy measurements, including patient global assessment of pain, patient and investigator global assessment of disease activity, and Stanford Health Assessment Questionnaire Disability Index (P<0.05 vs placebo). Compared with placebo, significantly fewer patients in the 25-mg and 50-mg rofecoxib groups discontinued therapy because of lack of efficacy (P = 0.02 and P = 0.032, respectively). Our results show that rofecoxib 25 and 50 mg once daily was effective and generally well-tolerated in patients with RA.

Adult↗
PubMed1999

Effect of specific COX-2 inhibition in osteoarthritis of the knee: a 6 week double blind, placebo controlled pilot study of rofecoxib. Rofecoxib Osteoarthritis Pilot Study Group.

OBJECTIVE: To determine the efficacy and safety of the cyclooxygenase 2 (COX-2) specific inhibitor, rofecoxib in patients with osteoarthritis (OA) of the knee. METHODS: Rofecoxib, 25 mg or 125 mg once daily, was compared with placebo in a 6 week, double blind, parallel group, randomized, multicenter study of 219 patients with knee OA. RESULTS: Both doses of rofecoxib produced clinically significant improvement as assessed by primary (e.g., WOMAC Pain Subscale 0-100 mm, decrease from baseline: placebo: 7.1 mm; rofecoxib 25 mg: 28.1 mm, rofecoxib 125 mg: 28.0 mm; p < 0.001 rofecoxib vs placebo) and secondary efficacy (p < 0.05) criteria compared with placebo. Clinical improvement with the 25 mg dose was similar to that with the 125 mg dose. Both rofecoxib doses were generally well tolerated. CONCLUSION: Specific inhibition of COX-2 by 25 and 125 mg rofecoxib, administered once daily, resulted in clinically meaningful improvements in patients with OA. This study confirms that COX-2 derived prostanoids are important clinical mediators of pain and other symptoms of knee OA and that inhibition of COX-1 is not required to provide clinical benefit.

Adult↗
PubMed1998

Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group.

BACKGROUND: Osteoporosis is a common complication of long-term glucocorticoid therapy for which there is no well-proved preventive or restorative treatment. METHODS: We carried out two 48-week, randomized, placebo-controlled studies of two doses of alendronate in 477 men and women, 17 to 83 years of age, who were receiving glucocorticoid therapy. The primary end point was the difference in the mean percent change in lumbar-spine bone density from base line to week 48 between the groups. Secondary outcomes included changes in bone density of the hip, biochemical markers of bone turnover, and the incidence of new vertebral fractures. RESULTS: The mean (+/-SE) bone density of the lumbar spine increased by 2.1+/-0.3 percent and 2.9+/-0.3 percent, respectively, in the groups that received 5 and 10 mg of alendronate per day (P<0.001) and decreased by 0.4+/-0.3 percent in the placebo group. The femoral-neck bone density increased by 1.2+/-0.4 percent and 1.0+/-0.4 percent in the respective alendronate groups (P<0.01) and decreased by 1.2+/-0.4 percent in the placebo group (P<0.01). The bone density of the trochanter and total body also increased significantly in the patients treated with alendronate. There were proportionally fewer new vertebral fractures in the alendronate groups (overall incidence, 2.3 percent) than in the placebo group (3.7 percent) (relative risk, 0.6; 95 percent confidence interval, 0.1 to 4.4). Markers of bone turnover decreased significantly in the alendronate groups (P<0.001). There were no differences in serious adverse effects among the three groups, but there was a small increase in nonserious upper gastrointestinal effects in the group receiving 10 mg of alendronate. CONCLUSIONS: Alendronate increases bone density in patients receiving glucocorticoid therapy.

Adolescent↗
PubMed1998

Non-NSAID pharmacologic treatment options for the management of chronic pain.

Chronic pain affects 75 million US citizens. A number of pharmacologic treatments are available for chronic pain that does not respond adequately to nonpharmacologic methods. Long the mainstay of chronic pain management, nonsteroidal anti-inflammatory drugs (NSAIDs) are known to be associated with gastrointestinal (GI) and renal toxicities, a particular problem for the elderly population, which commonly experiences chronic pain, such as that associated with osteoarthritis (OA). Several non-NSAID, non-narcotic therapies are available for noninflammatory pain. Acetaminophen is as effective as NSAIDs for the management of mild-to-moderate OA pain and is the recommended first-line therapy by the American College of Rheumatology (ACR). Propoxyphene, widely believed to be safe and effective, may, in fact, be no more effective-and perhaps less effective-than acetaminophen or ibuprofen. A relatively new analgesic, tramadol, appears to be a useful therapy for patients who do not receive adequate pain relief with acetaminophen and are at risk for NSAID-related side effects. For localized chronic pain associated with OA, topical capsaicin is also an effective analgesic.

Acetaminophen↗
PubMed1998

Knee adduction moment, serum hyaluronan level, and disease severity in medial tibiofemoral osteoarthritis.

OBJECTIVE: The adduction moment at the knee during gait is the primary determinant of medial-to-lateral load distribution. If the adduction moment contributes to progression of osteoarthritis (OA), then patients with advanced medial tibiofemoral OA should have higher adduction moments. The present study was undertaken to investigate the hypothesis that the adduction moment normalized for weight and height is associated with medial tibiofemoral OA disease severity after controlling for age, sex, and pain level, and to examine the correlation of serum hyaluronan (HA) level with disease severity and with the adduction moment in a subset of patients. METHODS: Fifty-four patients with medial tibiofemoral OA underwent gait analysis and radiographic evaluation. Disease severity was assessed using the Kellgren-Lawrence (K-L) grade and medial joint space width. In a subset of 23 patients with available sera, HA was quantified by sandwich enzyme-linked immunosorbent assay. Pearson correlations, a random effects model, and multivariate regression models were used. RESULTS: The adduction moment correlated with the K-L grade in the left and right knees (r = 0.68 and r = 0.60, respectively), and with joint space width in the left and right knees (r = -0.45 and r = -0.47, respectively). The relationship persisted after controlling for age, sex, and severity of pain. The partial correlation between K-L grade and adduction moment was 0.71 in the left knees and 0.61 in the right knees. For every 1.0-unit increase in adduction moment, there was a 0.63-mm decrease in joint space width. In the subset of patients in whom serum HA levels were measured, HA levels correlated with medial joint space width (r = -0.55), but not with the adduction moment. CONCLUSION: There is a significant relationship between the adduction moment and OA disease severity. Serum HA levels correlate with joint space width but not with the adduction moment. Longitudinal studies will be necessary to determine the contribution of the adduction moment, and its contribution in conjunction with metabolic markers, to progression of medial tibiofemoral OA.

Aged↗
PubMed1998

Chronic low back pain: new perspectives and treatment guidelines for primary care: Part I.

Low back pain is a leading cause of work-related disability and has important socioeconomic consequences. Although there is little evidence to determine the optimal treatment of chronic low back pain, treatment goals can be established. Primary care providers should focus on pain management, improvement of activity and functional level, and fostering a greater understanding of chronic low back pain. This two-part article summarizes consensus guidelines developed by practitioners with expertise in pain management, family medicine, internal medicine, physical therapy, rheumatology, and managed care, and provides direction for primary care providers on a multidisciplinary approach to the patient with chronic low back pain.

Absenteeism↗
PubMed1998

Chronic low back pain: new perspectives and treatment guidelines for primary care: Part II.

Low back pain is a leading cause of work-related disability and has important socioeconomic consequences. Although there is little evidence to determine the optimal treatment of chronic low back pain, treatment goals can be established. Primary care providers should focus simultaneously on pain management, improvement of activity and functional level, and fostering a greater understanding of chronic low back pain. This two-part article summarizes consensus guidelines developed by practitioners with expertise in pain management, family medicine, internal medicine, physical therapy, rheumatology, and managed care and provides direction for primary care providers on a multidisciplinary approach to the patient with chronic low back pain. This part examines pharmacologic methods.

Analgesics↗
PubMed1997

Therapeutic approaches to osteoarthritis.

Management is multifaceted: Palliation of pain should be accompanied by physical and occupational therapy and use of adaptive devices to improve performance. New techniques aim to interrupt disease progression and to induce biologic repair.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Etodolac (Lodine) in the treatment of osteoarthritis: recent studies.

Etodolac (Lodine) has been marketed in the United States since 1991 for managing pain and for acute and longterm treatment of the signs and symptoms of osteoarthritis (OA). Etodolac was recently approved for the treatment of rheumatoid arthritis. We review the results of 3 recent 4 week, multicenter, placebo controlled, parallel group studies that compared the efficacy and safety of etodolac with naproxen and nabumetone. Because studies of etodolac in the treatment of OA concentrated on bid doses, the first study compared etodolac 800 mg/day given as 400 mg bid (106 patients) and 200 mg qid (105 patients) with naproxen 1000 mg/day (109 patients) and placebo (104 patients). Etodolac was as effective as naproxen, and the 2 dosage schedules of etodolac were comparable. The 2nd study compared etodolac 400 mg bid (86 patients) with naproxen 500 bid (82 patients) and placebo (86 patients). Etodolac was again found to be as effective as naproxen. The 3rd study compared etodolac 400 mg bid (91 patients) with nabumetone 1500 mg/day (89 patients) and placebo (90 patients). The results indicated that the efficacy of etodolac was comparable to that of nabumetone and resulted in significantly better scores at endpoint on the investigator's overall assessment and patient's global assessment. In all 3 studies there were no significant differences among the groups in the frequency of study events or premature discontinuations as a result of study events. The most common adverse event was digestive system disturbance, which was mild to moderate in severity. The results of these studies confirm the efficacy and safety of etodolac in managing the signs and symptoms of OA.

Administration, Oral↗
PubMed1997

Subcutaneous administration of CAMPATH-1H: clinical and biological outcomes.

OBJECTIVE: A 24 week study of subcutaneous (sq) dosing with titration of CAMPATH-1H (C1H) dose against the circulating CD4+ T cell count in patients with rheumatoid arthritis (RA) was undertaken to examine the safety, biologic activity, and clinical efficacy of this approach. METHODS: All patients met American Rheumatism Association (ARA) criteria for active RA. Patients received either 0.5 or 1.0 mg of C1H subcutaneously twice per week; dosing could be doubled after the first 8 weeks of treatment and subsequently following 4 week dose intervals for lack of clinical efficacy, but was discontinued any time the CD4+ T cell count fell below 400/mm3. Patients were evaluated weekly for 2 weeks and then biweekly for clinical and laboratory variables of safety, biological activity, and disease activity. RESULTS: Ten patients were treated, 6 in the 0.5 mg cohort and 4 in the 1.0 mg cohort. Four of ten patients had a 20% modified Paulus response (2 in each cohort) while taking drug; there were minimal side effects, primarily limited to local reaction at the injection site. All patients had a > 50% drop in circulating CD4+ T cells within the first 2 weeks of therapy, with no further significant reduction; only 1/6 patients in the 0.5 mg cohort had dose limiting CD4+ T cell depression vs 2/4 in the 1.0 mg cohort. All patients developed antibodies to C1H. Appearance of anti-C1H was temporarily associated with a halt in further reduction of CD4+ T cell count despite continued C1H administration. CONCLUSION: Subcutaneous administration of C1H in low doses (0.5 mg biweekly) was well tolerated and did not result in dose limiting CD4+ T cell depletion in 5 of 6 patients. Clinical efficacy was observed in some patients but could not be maintained, possibly due to the production of anti-C1H antibodies.

Alemtuzumab↗
PubMed1996

CAMPATH-1H in rheumatoid arthritis--an intravenous dose-ranging study.

Forty-one patients with active and refractory rheumatoid arthritis(RA) received a total of 100, 250 or 400 mg of CAMPATH-1H (CAMPATH is a trademark of Glaxo-Wellcome group companies, registered in the US Patent and Trademark Office) over 5 or 10 days in an open, uncontrolled study. Following therapy, patients were monitored for adverse effects and disease activity for 6 months. Therapy was associated with prolonged peripheral blood lymphopenia in all dosing cohorts. During the month immediately following therapy, lymphopenia was most profound in the 400 mg cohorts. The first dose of monoclonal antibody (Mab) was associated with a 'flu'-like syndrome, more pronounced at higher initial doses. One patient developed haemolytic-uraemic syndrome. There were a number of dose-related infections during the early post-treatment period and one fatal opportunistic infection which followed additional immunosuppressive therapy. Antiglobulin responses developed in 9 of 31 patients tested. The majority of patients showed symptomatic improvement following therapy and 20% of patients maintained a 50% Paulus response at 6 months, all of whom were in the 250 or 400 mg cohorts. CAMPATH-1H appears to be an effective treatment for RA. Allowing for the small number of patients treated, infections were more common with higher doses, although this was not true for adverse events overall, and therapeutic responses were more sustained at higher dosing levels. The broad specificity of CAMPATH-1H may be appropriate for the immunotherapy of RA and future studies should aim to define a dose with an optimal therapeutic ratio.

Alemtuzumab↗
PubMed1996

Viral arthritis.

Viral infections can present with different patterns of joint and soft tissue involvement, and the etiologic role of viruses in various rheumatic diseases is a subject of continued great interest. Recently, new immunoenzymatic assays have brought a better understanding of the relationship between hepatitis C virus serotypes and their immunologic manifestations. Our knowledge of the consequences of parvovirus B19 infection has broadened to include the variable clinical spectrum the role of inflammatory cytokine production in parvovirus-induced arthritis, a postulated causative role for B19 in rheumatoid arthritis, and a negative association between parvovirus and Still's disease as well as chronic fatigue syndrome. New, specific antibodies to nonstructural protein NS-1 in parvovirus B19-associated arthritis have been detected. Arthritis related to hepatitis B virus vaccination or measles and mumps vaccination was also reported. The papers reviewed here demonstrate the continuing efforts in defining the etiopathogenesis of virus-induced rheumatic diseases.

Arthritis, Infectious↗
PubMed1995

Guidelines for the medical management of osteoarthritis. Part I. Osteoarthritis of the hip. American College of Rheumatology.

Treatment of patients with OA of the hip should be individualized and tailored to the severity of the disease. In individuals with mildly symptomatic disease, treatment may be limited to patient education, physical and occupational therapy, other nonpharmacologic modalities, and drug therapy with a non-opioid oral analgesic. In patients who are unresponsive to this treatment regimen, the use of an NSAID in addition to nonpharmacologic therapy is appropriate unless it is medically contraindicated. Patients with severe symptomatic OA of the hip require an aggressive approach to decreasing pain, increasing mobility, and improving function; such patients may benefit from orthopedic consultation and evaluation for osteotomy or total joint arthroplasty.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Guidelines for the medical management of osteoarthritis. Part II. Osteoarthritis of the knee. American College of Rheumatology.

Treatment of patients with OA of the knee should be individualized and tailored to the severity of the symptoms. In individuals with mild symptomatic OA, treatment may be limited to patient education, physical and occupational therapy and other nonpharmacologic modalities, and pharmacologic therapy including non-opioid oral and topical analgesics. In patients who are unresponsive to this treatment regimen, the use of NSAIDs in addition to nonpharmacologic therapy is appropriate unless medically contraindicated. Judicious use of intraarticular steroid injections has a role either as monotherapy or an adjunct to systemic therapy in patients with knee OA who have symptomatic effusions. The role of joint lavage and arthroscopic debridement in patients with OA of the knee who are unresponsive to conservative medical therapy needs further study, and these procedures cannot be routinely recommended for all patients at this time. Patients with severe symptomatic OA of the knee require an aggressive approach to decreasing pain, increasing mobility, and decreasing functional impairment; such patients may benefit from orthopedic consultation and evaluation for osteotomy or total joint arthroplasty.

Administration, Topical↗
PubMed1995

NSAIDs in orthopaedic practice: management guidelines for arthritis patients.

Guidelines are provided for prescribing nonsteroidal antiinflammatory drugs (NSAIDs) pre- and postoperatively for arthritis patients. Most NSAIDs impair platelet aggregation and prolong bleeding time, increasing the risk of complications during and immediately following surgery; thus, the effects of individual NSAIDs must be considered prior to surgery. Postoperative treatment issues that must be considered include gastrointestinal safety, renal and hepatic safety, safety in the elderly, and efficacy of various NSAIDs. Various strategies to improve gastrointestinal safety, including use of NSAIDs with low ulcerogenic potential such as nabumetone, low-dose ibuprofen, and etodolac, are discussed. As all NSAIDs can reduce pain and inflammation, selection of a particular NSAID should be based on careful consideration of pharmacologic and clinical differences.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Severity of articular cartilage abnormality in patients with osteoarthritis: evaluation with fast spin-echo MR vs arthroscopy.

OBJECTIVE: The purpose of this study was to assess the accuracy of fast spin-echo MR imaging for depicting the severity of articular cartilage abnormalities in patients with osteoarthritis. SUBJECTS AND METHODS: Twenty-three subjects (10 volunteers less than 35 years old and 13 patients with proved, symptomatic, idiopathic osteoarthritis of the knee of 6 months' to 10 years' clinical duration) underwent fast spin-echo MR imaging of the knee. Two observers graded each articular surface using a five-category scale that took into account abnormalities in the signal intensity of cartilage as well as thickness and contour. The 13 patients also underwent arthroscopic evaluation (as part of a separate protocol) in which cartilage abnormalities were graded by using a similar five-category grading scale, without the graders knowing the results of MR imaging. Articular cartilage was assumed to be normal in the volunteers. RESULTS: One hundred thirty-seven joint surfaces were graded; one surface was obscured by artifact and was excluded. The Spearman rank linear correlation between arthroscopic and MR grading was highly significant (p < .002) for each of the six articular regions evaluated. The MR and arthroscopic grades were the same in 93 (68%) of 137 joint surfaces, they were the same or differed by one grade in 123 surfaces (90%), and they were the same or differed by one or two grades in 129 surfaces (94%). CONCLUSION: Our results suggest that fat-presaturated fast spin-echo MR imaging depicts the severity of articular cartilage abnormalities in osteoarthritis with reasonable accuracy, as compared with arthroscopic evaluation as the standard of reference.

Adult↗
PubMed1993

Effect of piroxicam on gait in patients with osteoarthritis of the knee.

OBJECTIVE: To determine whether the use of a nonsteroidal antiinflammatory drug (NSAID) in patients with painful osteoarthritis (OA) of the knee would result in alterations in specific biomechanical parameters of gait. METHODS: Eighteen patients with symptomatic knee OA and varus knee deformity underwent initial clinical evaluation for pain and activities of daily living, and assessment of parameters of gait utilizing a well-described computerized system. All patients were then treated with piroxicam at 20 mg once daily, and clinical and gait analyses were repeated after 4 weeks. RESULTS: Fifteen of the 18 patients studied had a significant increase in the knee adduction moment after treatment. In the group as a whole there was a significant increase in knee adduction moment (mean percent body weight times height [%BWTH] 4.11 pretreatment versus 4.57 after 4 weeks of treatment; P < 0.01) and maximum quadriceps moment (mean %BWTH 2.13 pretreatment, 2.62 posttreatment; P < 0.01), as well as changes in other gait parameters that might be expected to be altered as a result of relief of pain. Sixteen of 18 patients experienced symptomatic relief, with a significant reduction in pain in the group as a whole after 4 weeks (P < 0.001). CONCLUSION: NSAID treatment in patients with knee OA results in a reduction in symptomatic pain and an increase in loading of the knee. Whether the increased loading is due to the analgesic effects of the treatment is unknown, but if so, the development of agents capable of relieving pain while reducing loads at the knee may be desirable.

Adult↗