A 4-week randomized study of acetaminophen extended-release vs rofecoxib in knee osteoarthritis.

OBJECTIVE: To compare the safety and efficacy of acetaminophen extended-release (APAP ER) with rofecoxib for the management of pain associated with knee osteoarthritis (OA). METHODS: Four hundred and three adult patients with moderate pain secondary to knee OA were randomized to receive APAP ER 1300 mg three times daily, rofecoxib 12.5mg once daily, or rofecoxib 25mg once daily. Primary end point was change from baseline at week 4 in the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale score using a visual analog scale. This 4-week study was conducted at 23 US research sites from October 1999 to October 2000. RESULTS: APAP ER was noninferior to rofecoxib 12.5mg because the upper 95% confidence limit (CL) for the least squares mean (LSM) change from baseline (35.27 mm at week 4) did not exceed the prespecified noninferiority limit of 50mm. The upper CL (57.39 mm) exceeded the noninferiority limit for APAP ER compared with rofecoxib 25mg at week 4. There were no significant differences among groups in the overall incidence of adverse events. CONCLUSION: APAP ER 3900 mg daily was noninferior to rofecoxib 12.5mg daily, but noninferiority was not established to rofecoxib 25mg daily. APAP ER was well tolerated and no safety issues were identified. Based on the results of this study, APAP ER 3900 mg daily is an alternative to nonsteroidal anti-inflammatory drugs (NSAIDs), such as rofecoxib, in treating pain associated with knee OA.

Evaluating the adequacy of disease control in patients with rheumatoid arthritis: a RAND appropriateness panel.

OBJECTIVES: There is a lack of agreement on assessing disease activity in patients with RA and determining when the RA treatment should be changed or continued. A panel of rheumatologists was convened to develop guidelines to assess adequacy of disease control, focusing on the use of disease-modifying anti-rheumatic drugs. METHODS: The Research and Development/University of California in Los Angeles (RAND/UCLA) Appropriateness Method was used to evaluate disease control adequacy. After a literature review, 108 scenarios were developed to simulate situations most likely to be encountered in clinical practice and rated on a 9-point scale by a 10-member expert panel. RESULTS: Final appropriateness rankings for the scenarios were as follows: 37% 'appropriate', 48% 'inappropriate', and 16% 'neutral'. The panelists felt that patients with disease control in the 'appropriate' range have adequate control with their current therapy, whereas those in the 'inappropriate' range should be considered for a change in therapy. Those in 'neutral' areas should have their therapy reviewed carefully. The panelists recommended that the clinically active joint count should be considered the most important decision factor. In patients with no clinically active joints, regardless of other factors no change in therapy was felt to be warranted. Patients with five or more active joints should be considered inadequately treated, and in patients with one to four active joints other variables must be considered in the decision to change therapy. CONCLUSION: These preliminary guidelines will assist the clinician in determining when a patient's clinical situation warrants therapy escalation and when continuing the current regimen would be appropriate.

A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis.

BACKGROUND: Etanercept, which blocks the action of tumor necrosis factor, reduces disease activity in patients with long-standing rheumatoid arthritis. Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is unknown. METHODS: We treated 632 patients with early rheumatoid arthritis with either twice-weekly subcutaneous etanercept (10 or 25 mg) or weekly oral methotrexate (mean, 19 mg per week) for 12 months. Clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology. Bone erosion and joint-space narrowing were measured radiographically and scored with use of the Sharp scale. On this scale, an increase of 1 point represents one new erosion or minimal narrowing. RESULTS: As compared with patients who received methotrexate, patients who received the 25-mg dose of etanercept had a more rapid rate of improvement, with significantly more patients having 20 percent, 50 percent, and 70 percent improvement in disease activity during the first six months (P<0.05). The mean increase in the erosion score during the first 6 months was 0.30 in the group assigned to receive 25 mg of etanercept and 0.68 in the methotrexate group (P= 0.001), and the respective increases during the first 12 months were 0.47 and 1.03 (P=0.002). Among patients who received the 25-mg dose of etanercept, 72 percent had no increase in the erosion score, as compared with 60 percent of patients in the methotrexate group (P=0.007). This group of patients also had fewer adverse events (P=0.02) and fewer infections (P= 0.006) than the group that was treated with methotrexate. CONCLUSIONS: As compared with oral methotrexate, subcutaneous [corrected] etanercept acted more rapidly to decrease symptoms and slow joint damage in patients with early active rheumatoid arthritis.

Antipolymer antibody reactivity in a subset of patients with fibromyalgia correlates with severity.

OBJECTIVE: To determine the prevalence of antipolymer antibodies (APA) in patients with fibromyalgia (FM) and autoimmune disease control groups and to determine if the presence of these antibodies correlates with severity in patients with FM. METHODS: Sera from patients with FM (n = 47), osteoarthritis (OA) (n = 16), and rheumatoid arthritis (RA) (n = 13) were analyzed. Patients with implants of any kind and patients with concurrent autoimmune conditions were excluded from study. Banked sera from autoimmune disease controls including poly/dermatomyosis (n = 15), RA (n = 30), systemic lupus erythmatosus (SLE) (n = 30), and systemic sclerosis (SSc) (n = 30) were also analyzed. To determine if seroreactivity correlates with severity, banked sera from patients with FM assessed as severe (n = 28) or mild (n = 37) and from controls (n = 21) were assayed. RESULTS: Following analysis, the prevalence of seroreactivity was found to be higher in patients with FM (22/47, 47%) compared to patients with OA (3/16, 19%; p<0.1) or RA (1/13, 8%; p<0.05) and the autoimmune disease control sera from poly/dermatomyosis (2/15, 13%; p<0.05), and patients with RA (3/30, 10%; p<0.01), SLE (1/30, 3%; p<0.01), and SSc (1/30, 3%; p<0.01). The prevalence of APA seroreactivity was also significantly higher in patients with severe FM (17/28, 61%) compared to patients with mild FM (11/37, 30%; p<0.05) and controls (4/21, 19%; p<0.01). In addition, both mean threshold and mean tolerance dolorimetry scores were significantly lower in the seropositive patients with mild FM (1.33+/-0.21, 1.95+/-0.25, respectively) compared to the seronegative patients (1.83+/-0.08, 2.53+/-0.11; p<0.05 for both comparisons, respectively). CONCLUSION: These results reveal that an immunological response, production of anti-polymer antibodies, is associated with a subset of patients with FM. The results also suggest that the APA assay may be an objective marker in the diagnosis and assessment of FM and may provide additional avenues of investigation into the pathophysiological processes involved in FM.

Use of antipolymer antibody assay in recipients of silicone breast implants.

BACKGROUND: Local complications (encapsulation, rashes, rupture, and leakage) can occur after placement of silicone gel-containing breast implants (SBI). Whether SBI exposure results in systemic manifestations in some recipients is controversial. We have carried out a blinded study to assess whether there is any difference between SBI recipients and non-exposed controls in the proportions positive for serum antibodies directed against polymeric substances. METHODS: We recruited female SBI recipients (including those without symptoms) who presented to a single rheumatology clinic. A physician global assessment was used to classify SBI recipients who did not meet criteria for specific autoimmune diseases according to the severity of local and systemic signs and symptoms. Controls were recruited from among clinic staff and their acquaintances. Results of the antipolymer antibody (APA) assay were compared with those of an assay for antinuclear antibodies (ANA) and with the severity of the signs and symptoms. FINDINGS: Positive APA results were found in one (3%) of 34 SBI recipients with limited symptoms, two (8%) of 26 with mild symptoms, seven (44%) of 16 with moderate symptoms, and 13 (68%) of 19 with advanced symptoms. Four (17%) of 23 healthy non-SBI-exposed controls and two (10%) of 20 non-exposed women with classic autoimmune diseases were positive for APA. Thus, women with moderate or advanced symptoms were significantly more likely than those with limited or mild symptoms, or non-exposed controls to have APA (p < 0.001). The proportion with positive ANA results was higher for women with classic autoimmune diseases 14 (70%) of 20 than for any SBI-exposed subgroup (0-33%). INTERPRETATION: The APA assay can objectively contribute to distinguishing between SBI recipients with limited or mild signs and symptoms. SBI recipients with more severe manifestations, and patients with specific autoimmune diseases. Further studies will be needed to define the signs and symptoms associated with exposure to SBI.

The clinical significance of anticytoplasmic antibodies found on fluorescent antinuclear antibody testing.

We evaluated anticytoplasmic antibodies (FACA) found on immunofluorescent antinuclear antibody tests (FANA). Of 1830 sera submitted to our laboratory for FANA testing, we found a 2.7% incidence of FACA as compared to a 21.5% incidence of FANA. Patients with FACA had rheumatologic and other systemic diseases closely resembling those present in controls with FANA, indicating that FACA provide a pathologic marker independent of FANA. Among FACA+ patients studied further, 59% were found to have serum antibodies to mitochondrial (Mit) and/or smooth muscle (SMus) antigens, largely in the absence of liver disease. By contrast, sera from FANA+ controls lacked anti-Mit and anti-SMus antibodies, but did contain antibodies to SSA, SSB, dsDNA, Sm, and RNP in much higher frequency than FACA+ sera.