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1.
J Rheumatol ; 28(1): 47-53, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11196542

ABSTRACT

OBJECTIVE: Rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS) are associated with an increased risk of lymphoma. Epstein-Barr virus (EBV), a ubiquitous herpes virus, has been linked etiologically to lymphoma in patients with RA and primary SS. Recently, methotrexate (MTX) has also been linked to the development of these lymphomas. We investigated the frequency of EBV in lymphoma tissue of patients with RA and primary SS and the association of MTX with lymphomagenesis. METHODS: Twenty-three patients with RA and 9 with primary SS with a history of lymphoma were identified by writing to all Arthritis Foundation member rheumatologists in Washington State. Formalin fixed, paraffin embedded tissue blocks were then requested from pathology laboratories. Lymph nodes from 5 RA patients without lymphoma were also studied. In situ hybridization using a biotinylated EBER-1 oligonucleotide probe was used to detect EBV in tissue sections. Positive and negative laboratory controls were used to ensure procedural integrity. RESULTS: Specimens from 21 RA patients were obtained, with 2 subsequently excluded due to specimen quality. Specimens from 6 patients with primary SS were obtained. In situ hybridization for EBV was positive in 5/19 (26%) RA patients and 1/6 patients with primary SS. In the nonmalignant lymph nodes no patient showed EBV. One primary SS and 12 RA patients were known to be taking MTX at the time of lymphoma diagnosis. Of the EBV positive RA lymphoma patients, 4/5 were receiving MTX at the time of diagnosis. These results show that EBV is present in lymphoma tissue of some patients with RA and very few with primary SS. CONCLUSION: EBV is over-represented in the lymphomas of patients with RA, but whether MTX plays a role in predisposing patients with RA and primary SS to the development of lymphoma, perhaps by influencing behavior of EBV, remains unclear.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/pathology , Epstein-Barr Virus Infections/pathology , Herpesvirus 4, Human/isolation & purification , Immunocompromised Host , Lymphoma/pathology , Methotrexate/therapeutic use , Sjogren's Syndrome/pathology , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Epstein-Barr Virus Infections/complications , Female , Herpesvirus 4, Human/pathogenicity , Humans , In Situ Hybridization , Lymph Nodes/pathology , Lymph Nodes/virology , Lymphoma/virology , Male , Middle Aged , RNA, Viral/analysis , Sjogren's Syndrome/complications , Sjogren's Syndrome/drug therapy
2.
J Rheumatol ; 26(4): 816-25, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10229402

ABSTRACT

OBJECTIVE: (1) To review the diagnoses after 10 years in patients who were identified within 12 months of the onset of well established and undifferentiated connective tissue diseases (CTD). (2) To examine the death rates and disease remissions in these patients. METHODS: This inception cohort of 410 patients had less than one year of signs and/or symptoms of CTD. Diagnoses of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and poly/dermatomyositis (PM/DM) were made in 197 patients using accepted diagnostic and classification criteria. Diagnoses of undifferentiated CTD were made in 213 patients. These latter patients were placed in 3 categories: isolated Raynaud's phenomenon (RP), unexplained polyarthritis (UPA), and undifferentiated CTD (UCTD), defined as meeting at least 3 of 11 specific manifestations of CTD. The diagnoses and remissions in all patients after 10 years were determined. RESULTS: Patients with well established CTD tended to remain with the original diagnosis. The 10 year survival was at least 87% in all diagnostic categories, with the exception of SSc, in which it was 56%. The progression of UPA to RA occurred infrequently. The presence of antinuclear antibodies suggested that UPA may develop additional symptoms and/or a specific diagnosis, and RP in these patients increased the likelihood of progressing to UCTD or a specific well established CTD. Ten percent of patients with RP progressed to SSc. In patients with UCTD, joint pain/tenderness and swelling counts were associated with progression to other diagnoses including RA, while either serositis, malar rash, or discoid lupus suggested the eventual diagnosis of SLE. CONCLUSION: The survival of patients with SSc was poor, with most dying early in the course of their disease. Remissions were seen in all groups of patients except SSc. The remissions were sometimes transient in SLE. Undifferentiated disease at initial examination within 12 months of onset usually remains undifferentiated.


Subject(s)
Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/mortality , Connective Tissue Diseases/therapy , Diagnostic Errors , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Remission Induction , Severity of Illness Index , Sex Distribution , Survival Rate
3.
J Rheumatol ; 25(2): 261-8, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9489817

ABSTRACT

OBJECTIVE: To review the diagnoses after 5 years in patients who were identified within 12 months of the onset of well established and undifferentiated connective tissue diseases (CTD); to examine death rates and disease remissions in these patients. METHODS: This inception cohort of 410 patients was identified in 10 academic rheumatology practices. They had less than one year of signs and/or symptoms of CTD. Diagnoses of specific well established CTD were made using accepted diagnostic and classification criteria. The diagnoses after 5 years were determined. RESULTS: Patients with well established CTD tended to remain with the original diagnosis. The progression of unexplained polyarthritis to rheumatoid arthritis occurred infrequently. Ten percent of patients with isolated Raynaud's phenomenon progressed to systemic sclerosis (SSc). The 5 year survival was over 90% in all diagnostic categories, with the exception of SSc, in which it was 64%. CONCLUSION: Patients with a well established CTD usually continued with the same diagnosis. Patients with undifferentiated CTD tended to remain undifferentiated or to remit.


Subject(s)
Connective Tissue Diseases/diagnosis , Arthritis/diagnosis , Arthritis/mortality , Cohort Studies , Connective Tissue Diseases/mortality , Disease Progression , Follow-Up Studies , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/mortality , Prognosis , Raynaud Disease/diagnosis , Raynaud Disease/mortality , Rheumatic Diseases/diagnosis , Rheumatic Diseases/mortality , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/mortality
4.
J Rheumatol ; 24(10): 1896-902, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9330929

ABSTRACT

OBJECTIVE: To evaluate the ability of hydroxychloroquine sulfate (HCQ) to extend the response to combination therapy with HCQ and methotrexate (MTX) and the safety of longterm HCQ maintenance therapy in patients with active rheumatoid arthritis (RA). METHODS: Two-part study consisting of an open label segment evaluating combination HCQ/MTX therapy followed by a double blind segment evaluating maintenance therapy for a total of 60 weeks. First, all patients were treated with HCQ 400 mg/day and MTX 7.5 to 15 mg/week for 24 weeks. Then, responders were randomized into 3 groups: (1) HCQ with MTX as needed for disease flare (n = 40), (2) HCQ 400 mg/day (n = 41), or (3) placebo with MTX as needed for disease flare (n = 40), each for 36 weeks. RESULTS: Clinical disease and laboratory variables improved significantly during initial combination therapy with HCQ and MTX. After MTX withdrawal, HCQ-containing maintenance regimens delayed the onset of disease flare (p = 0.023). There were no unexpected adverse events at any time or between-group differences in the distribution of adverse events during the double blind segment. CONCLUSION: Combination of HCQ and MTX appeared to be effective and well tolerated for 24 weeks. After withdrawal of MTX, HCQ extended the response seen with combination therapy and was well tolerated for 36 weeks. Initial therapy with HCQ and MTX, followed by maintenance HCQ, may be a useful alternative for the treatment of RA.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Hydroxychloroquine/administration & dosage , Methotrexate/administration & dosage , Aged , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Time Factors , Treatment Outcome
5.
J Rheumatol Suppl ; 44: 64-8, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8833056

ABSTRACT

To assess the relative efficacy of methotrexate (MTX), azathioprine (AZA), and their combination in the treatment of rheumatoid arthritis (RA), a double blind, prospective, multicenter, controlled trial was carried out. Two hundred nine patients with active RA were treated with escalating doses of MTX (5-15 mg/week), AZA (50-150 mg/day), or combination (5/50-7.5/100) with opportunity to increase dosage at 6 week intervals. Patients were evaluated for clinical and laboratory improvement and assessed for radiologic progression at 48 weeks. One hundred ten patients remained on the initial, randomly assigned therapy. Response was defined as 30% or greater improvement in at least 3 of 4 variables, and occurred in the following: 38% on the combination arm, 26% on AZA, and 45% on MTX (p = 0.06). A trend for decreased radiologic progression was seen in the MTX group. Adverse experiences and treatment termination occurred more frequently in the combination and AZA arms relative to the MTX group. The most frequent causes for treatment discontinuations were lack of effectiveness, gastrointestinal adverse effects and liver enzyme elevation. This study establishes that the combination of MTX and AZA in the dosages employed is not associated with more toxicity than treatment with single agents, but enhanced efficacy is not seen. A trend toward decreased radiographic progression was noted in the MTX treated patients.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Azathioprine/therapeutic use , Methotrexate/therapeutic use , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/diagnostic imaging , Arthrography , Azathioprine/administration & dosage , Azathioprine/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Prospective Studies
6.
Arthritis Rheum ; 39(3): 403-14, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8607889

ABSTRACT

OBJECTIVES: To examine the musculoskeletal manifestations in a large cohort of patients (n = 410) diagnosed with either a well-established connective tissue disease (CTD) (n = 197) or an early undifferentiated CTD (n = 213) with a symptom duration of <1 year. This study was aimed at determining the predictive value of demographic, clinical, and laboratory features on outcome in patients with unexplained polyarthritis (UPA) (from the early undifferentiated CTD cohort; n = 67) or rheumatoid arthritis (RA) (from the well-established CTD cohort; n = 57), over a 5-year followup period. METHODS: Patients from both cohorts were assessed at years 1, 3, and 5. At the study visits, clinical data were collected in a standardized manner, and sera were obtained and stored. A priori criteria were established for patient ascertainment and diagnosis over the duration of the study. Standard statistics were used for comparisons of baseline characteristics in patients diagnosed as having systemic lupus erythematosus, RA, undifferentiated CTD, and UPA at entry into the cohorts. Baseline features in patients with UPA were examined according to the different subsequent outcomes (RA, CTD, or undifferentiated CTD, remission [nonpersistent], or persistent or active UPA). Baseline features in patients with RA whose disease remained active versus those in whom remission was attained were also examined. Two multivariable analyses, classification trees and polychotomous logistic regression, were performed to predict disease outcomes over time. RESULTS: The overall rate of ascertainment for the 410 patients ranged from 90 % at year 1 to 71 % at year 5. Patients with established CTDs showed a tendency for more stable diagnoses than those with early undifferentiated CTDs (90-100% versus 45-70%). Consistent baseline predictors of persistent active disease among patients with RA, in both univariate and multivariable analyses, were higher joint counts for pain and tenderness and higher erythrocyte sedimentation rate (ESR). In approximately 20% of patients who were classified as having RA when they originally entered the cohort, the disease was in remission at 5 years. Twenty percent of the patients originally classified as having UPA developed RA over the duration of the study. These patients tended to be older and to have swelling of small joints at baseline. However, a consistent pattern of predictive variables could not be identified in the multivariable analyses, other than at year 1 (higher small joint counts for swelling and higher ESR). CONCLUSION: Baseline features (joint counts, and ESR) among RA patients were variously predictive of persistently active disease at years 1-5. Consistent baseline predictors of outcome among patients with UPA only emerged at year 1. Remission occurred in approximately 20% of RA patients, whereas a similar percentage of patients with UPA developed RA. These findings have implications with regard to treatment decisions in patients with early RA and/or UPA.


Subject(s)
Connective Tissue Diseases/diagnosis , Adult , Aged , Arthritis/diagnosis , Arthritis, Rheumatoid/diagnosis , Cohort Studies , Connective Tissue Diseases/therapy , Female , Follow-Up Studies , Humans , Joint Diseases/diagnosis , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Musculoskeletal Diseases/diagnosis , Predictive Value of Tests , Recurrence , Time Factors , Treatment Outcome
7.
Scand J Rheumatol ; 25(6): 345-51, 1996.
Article in English | MEDLINE | ID: mdl-8996468

ABSTRACT

The present double-blind, placebo-controlled study was conducted to compare the safety and efficacy of tenidap in patients with rheumatoid arthritis (RA). Patients with flare of active RA following NSAID withdrawal were randomized to receive either placebo (n = 67) or tenidap (n = 131; 40-200 mg/day). The mean changes from baseline in efficacy and biochemical variables were compared between treatment groups at endpoint (4 weeks). The improvements in four of the five primary efficacy variables were significantly greater in the tenidap group compared with the placebo group (p < 0.01). Tenidap was also associated with an 18% reduction in erythrocyte sedimentation rate (ESR) and a marked, 51%, reduction in serum C-reactive protein (CRP) level, both of which were significantly greater than the changes in the placebo group (p < 0.05). The percentage of patients who discontinued because of side effects was the same in both groups (3%). In conclusion, tenidap 40-200 mg/day was effective and well tolerated in the treatment of patients with RA for 4 weeks.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Rheumatoid/drug therapy , Cyclooxygenase Inhibitors/therapeutic use , Indoles/therapeutic use , Administration, Oral , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cyclooxygenase Inhibitors/administration & dosage , Cyclooxygenase Inhibitors/adverse effects , Digestive System/drug effects , Double-Blind Method , Female , Humans , Indoles/administration & dosage , Indoles/adverse effects , Male , Middle Aged , Oxindoles , Treatment Outcome
8.
Arthritis Rheum ; 38(12): 1799-806, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8849352

ABSTRACT

OBJECTIVE: To assess the relative efficacy of methotrexate (MTX), azathioprine (AZA), and their combination in the treatment of rheumatoid arthritis (RA) in a double-blind, prospective, multicenter, controlled trial. METHODS: Two hundred nine patients with active RA were treated with escalating doses of MTX (5-15 mg/week), AZA (50-150 mg/day), or combination (5mg MTX/week plus 50 mg AZA/day-7.5 mg MTX/week plus 100 mg AZA/day), with opportunity to increase the dosage at 6-week intervals. The patients were evaluated for significant clinical and laboratory improvement and assessed for radiologic progression at 48 weeks. RESULTS: One hundred ten patients remained on the initial, randomly assigned therapeutic regimen. The percentage of patients who were responders, defined as those who had 30% or greater improvement in at least 3 of 4 variables, was 38% for the combination treatment, 26% for AZA, and 45% for MTX (P = 0.06). A trend toward decreased radiologic progression was seen in the MTX-treated patients. Termination of treatment due to adverse experience occurred more frequently with combination and AZA treatments than with MTX treatment. Lack of effectiveness, adverse gastrointestinal effects, and liver enzyme elevation were the most frequent causes of treatment discontinuation. CONCLUSION: This study establishes that the combination of MTX and AZA in the dosages utilized is not associated with more toxicity than treatment with single agents; however, enhanced efficacy is also not seen. There is a trend toward decreased radiologic progression in patients treated with MTX.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Azathioprine/therapeutic use , Methotrexate/therapeutic use , Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnostic imaging , Arthrography , Azathioprine/administration & dosage , Blood Sedimentation , Cross-Over Studies , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Methotrexate/administration & dosage , Middle Aged , Prospective Studies , Treatment Outcome , United States
9.
J Rheumatol ; 22(10): 2001-3, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8992008

ABSTRACT

In recent years there have been many significant developments in the ability to process radiographic pictures and transfer the images from one location to another, and we can now examine the application of computers in the radiographic evaluation of rheumatoid arthritis. Image management and communication systems can assist in providing better health care while lowering costs. Although this work is still in its infancy, the rapid growth in both hardware capability and software techniques will soon make these techniques available to physicians everywhere. The expanding capability in the commercial world is being embraced by the radiology department, and will soon allow rheumatologists to access images at greater distances, and do more with the images which become available.


Subject(s)
Arthritis, Rheumatoid/diagnostic imaging , Arthrography , Image Processing, Computer-Assisted/trends , Radiology Information Systems/trends , Telecommunications/trends , Humans
10.
J Rheumatol ; 21(8): 1457-62, 1994 Aug.
Article in English | MEDLINE | ID: mdl-7983646

ABSTRACT

OBJECTIVE: To compare the relative safety and efficacy of hydroxychloroquine (HCQ) and placebo (Pl) in the treatment of the articular complaints of systemic lupus erythematosus (SLE). METHODS: Seventy-one patients with mild SLE requiring < or = 10 mg of prednisone or equivalent daily and with arthritis or arthralgias were entered into a 48-week prospective, controlled, double blind multicenter trial and randomly assigned to either HCQ or Pl. RESULTS: Both HCQ and Pl were well tolerated in the 48-week trial. There were no remissions. With the exception of the patient assessment of joint pain, all other joint measures were similar between the groups. Twenty-nine patients withdrew before the end of the trial although only 2 patients withdrew for adverse drug effects. CONCLUSION: Our study found subjective pain relief as the only statistically significant difference in joint count variables from HCQ in the treatment of the articular manifestations of SLE.


Subject(s)
Hydroxychloroquine/therapeutic use , Joint Diseases/drug therapy , Lupus Erythematosus, Systemic/drug therapy , Adult , Double-Blind Method , Female , Humans , Hydroxychloroquine/adverse effects , Lupus Erythematosus, Systemic/physiopathology , Male , Pain/drug therapy , Prospective Studies
11.
Arthritis Rheum ; 37(3): 316-28, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8129787

ABSTRACT

Methotrexate (MTX) has become an important drug in the treatment of rheumatoid arthritis (RA). The American College of Rheumatology convened a committee to assess the risks of development of clinically significant liver disease (CSLD) during MTX treatment, to evaluate the risk and role of surveillance liver biopsies, and to provide recommendations about monitoring patients for liver toxicity. The committee recommends obtaining liver blood tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, albumin, bilirubin), hepatitis B and C serologic studies, and other standard tests including complete blood cell count and serum creatinine tests prior to starting treatment with MTX. A pretreatment liver biopsy should be considered only for patients with a history of prior excessive alcohol consumption, persistently abnormal baseline AST values, or chronic hepatitis B or C infection. At intervals of every 4-8 weeks the AST, ALT, and albumin levels should be monitored. Routine surveillance liver biopsies are not recommended for RA patients receiving traditional doses of MTX. However, a biopsy should be performed if a patient develops persistent abnormalities on liver blood tests. These are defined as elevations (above the upper limit of laboratory normal) in the AST in 5 of 9 determinations within a given 12-month interval (6 of 12 if tests are performed monthly) or a decrease in serum albumin below the normal range. The recommendations for monitoring and selection of patients for liver biopsy identify patients at potential risk for CSLD, and thus significantly reduce the number or patients who would be exposed to this procedure. Close monitoring is essential to reduce the risk of unrecognized serious liver disease. These recommendations should be revised as necessary to reflect new and compelling information.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Chemical and Drug Induced Liver Injury , Liver/drug effects , Methotrexate/adverse effects , Biopsy/adverse effects , Biopsy/economics , Costs and Cost Analysis , Humans , Liver/pathology , Liver Diseases/pathology , Liver Function Tests , Risk Factors
12.
Arthritis Rheum ; 36(9): 1196-206, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8216413

ABSTRACT

OBJECTIVE: To compare the relative safety and efficacy of naproxen and acetaminophen in the treatment of osteoarthritis (OA) of the knee. The major outcome measures were radiographic progression and withdrawal from the trial due to lack of efficacy. METHODS: One hundred seventy-eight patients with OA of the knee were enrolled in a 2-year prospective, controlled, double-blind multicenter trial and were randomly assigned to receive acetaminophen (ACT) or naproxen (NPX) treatment. RESULTS: After 6 weeks of treatment, modest improvement in pain on motion and in physician's global assessment was seen in both the ACT and the NPX groups, and the NPX group also had modest improvement in pain at rest and in 50-foot walk time. Sixty-two patients completed the 2-year study. Among these patients, radiographic progression was similar in the 2 treatment groups. Withdrawal from the trial due to lack of drug efficacy was slightly more frequent among patients in the ACT group (22% versus 16%), but withdrawal due to adverse drug effects was slightly more common in the NPX group (23% versus 18%). CONCLUSION: The efficacy of ACT treatment and NPX treatment was similar, although it was slightly better for NPX. The toxicity rate was slightly lower with ACT. However, the high rate of withdrawal in both treatment groups suggests that neither is satisfactory for the treatment of OA.


Subject(s)
Acetaminophen/therapeutic use , Knee Joint , Naproxen/therapeutic use , Osteoarthritis/drug therapy , Acetaminophen/adverse effects , Adult , Aged , Aged, 80 and over , Arthrography , Double-Blind Method , Female , Humans , Knee Joint/diagnostic imaging , Knee Joint/physiopathology , Male , Middle Aged , Naproxen/adverse effects , Osteoarthritis/diagnostic imaging , Osteoarthritis/physiopathology , Patient Dropouts , Prospective Studies , Walking
13.
Ann Intern Med ; 118(8): 602-9, 1993 Apr 15.
Article in English | MEDLINE | ID: mdl-8452326

ABSTRACT

OBJECTIVE: To characterize the course of early scleroderma and to delineate prognostic factors present within 1 year of disease onset that might identify patients at high risk. DESIGN: Inception cohort study. SETTING: Ten university-based rheumatology clinics participating in the Cooperative Systematic Studies of Rheumatic Diseases Program. PATIENTS: Forty-eight patients who had had scleroderma for less than 1 year. MEASUREMENTS: Fifteen patients with early scleroderma who died were compared with those still living during the initial study period (1982 to 1992). Kaplan-Meier survival estimation and Cox proportional hazards analysis were used to analyze baseline variables for their ability to predict survival duration. RESULTS: Eight of 15 deaths were due to cardiac or pulmonary system failure. The estimated 5-year survival rate was 68%. Baseline factors that were the most predictive of a poor outcome included the presence of abnormal cardiopulmonary signs and abnormal urine sediment (pyuria, hematuria). CONCLUSION: Evidence of early cardiopulmonary disease, renal disease, inflammation, or immune activation may identify a subset of patients with scleroderma who will experience rapidly progressive disease and early death.


Subject(s)
Scleroderma, Systemic/mortality , Adult , Analysis of Variance , Female , Heart Diseases/mortality , Humans , Lung Diseases/mortality , Male , Middle Aged , Prognosis , Proportional Hazards Models , Prospective Studies , Receptors, Interleukin-2/analysis , Scleroderma, Systemic/metabolism , Scleroderma, Systemic/physiopathology , Survival Analysis , Time Factors
14.
J Rheumatol Suppl ; 36: 9-12, 1992 Nov.
Article in English | MEDLINE | ID: mdl-1474545

ABSTRACT

The availability of an ever expanding number of nonsteroidal antiinflammatory drugs (NSAID) relates to their utility for the treatment of a broad spectrum of disorders. Both the efficacy and adverse effects of NSAID relate primarily to their antiprostaglandin mechanism of action, prostaglandin inhibition. At full antiinflammatory doses, there is little evidence to support a rank order of effectiveness. The major differences among NSAID are their half-lives and safety profiles. With newer agents the emphasis is on safety, especially with respect to gastrointestinal irritation. Acknowledgment of inherent drug differences with respect to pharmacology and safety enhances tolerability by the patient and increases the likelihood for continued drug therapy.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Rheumatic Diseases/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/blood , Aspirin/therapeutic use , Drug Evaluation , Half-Life , Humans
15.
Arthritis Rheum ; 35(8): 849-56, 1992 Aug.
Article in English | MEDLINE | ID: mdl-1642652

ABSTRACT

OBJECTIVE: To compare the relative safety and efficacy of azathioprine (AZA), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Two hundred twelve patients with active RA were entered into a 24-week prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: One hundred fifty-eight patients finished 24 weeks of the study. There were no remissions seen but response rates were greater than 30% for all outcome measures. Combination therapy was not statistically superior to MTX therapy alone, but both combination therapy and MTX alone were superior to AZA alone when patients were analyzed by intent-to-treat and with withdrawals treated as therapy failures. If only patients who continued taking the therapy were analyzed, the mean improvement was greater for AZA therapy than for MTX, while the combination remained the most active. Adverse effects on the gastrointestinal tract and elevations of liver enzyme levels were the most frequent causes for discontinuations. CONCLUSION: Both combination therapy and MTX alone were superior to therapy with AZA alone for active RA but were not statistically different in their effect on outcome assessment.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Azathioprine/therapeutic use , Methotrexate/therapeutic use , Adult , Aged , Aged, 80 and over , Azathioprine/adverse effects , Digestive System/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Liver/drug effects , Liver/enzymology , Male , Methotrexate/adverse effects , Middle Aged , Statistics as Topic , Time Factors
16.
Arthritis Rheum ; 35(3): 259-69, 1992 Mar.
Article in English | MEDLINE | ID: mdl-1536666

ABSTRACT

OBJECTIVE: To compare the relative safety and efficacy of auranofin (AUR), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Three hundred thirty-five patients with active RA were entered into a 48-week, prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: Two hundred eleven patients completed the trial. No remissions were seen, and there were no statistically significant differences among the treatment groups in the clinical or laboratory variables measured. Patients taking AUR alone had a slower onset of response than did patients taking MTX alone or in combination. Withdrawals because of adverse drug reactions were slightly more common for those taking combination therapy, but the differences were not statistically significant. Withdrawals because of lack of response were more common for single-drug therapy, with the difference between AUR and the combination reaching statistical significance. No unexpected adverse drug effects were identified, and all reactions resolved without sequelae. CONCLUSION: Except for fewer withdrawals because of lack of response, combination therapy did not demonstrate any advantage in efficacy over single-drug treatment within the time frame of the study.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Auranofin/therapeutic use , Methotrexate/therapeutic use , Adolescent , Adult , Auranofin/adverse effects , Double-Blind Method , Drug Therapy, Combination , Humans , Leukopenia/chemically induced , Methotrexate/adverse effects , Middle Aged , Thrombocytopenia/chemically induced
17.
J Rheumatol ; 19(1): 186, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1556694
18.
Semin Arthritis Rheum ; 21(2 Suppl 1): 40-3, 1991 Oct.
Article in English | MEDLINE | ID: mdl-1749948

ABSTRACT

An attempt should be made to predict the most likely course of individual disease when a patient is first diagnosed as having rheumatoid arthritis (RA). Such a prediction can be called prognostic staging for therapy. While no specific marker will accomplish this accurately, the summation of demographic, genetic, historical, physical, laboratory, radiologic, and scanning data may be used to make a reasonable estimation of outcome. The use of immunogenetic typing is the newest technique that can help identify patients likely to develop more serious disease. Once patients are identified as having probable aggressive disease, that is, beyond stage I, combination therapy should be initiated. Goals of therapy should include the prevention and/or interference of progression of radiologic erosions, as well as functional improvement as measured by life-style and productivity.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/physiopathology , Humans , Immunogenetics/methods , Prognosis , Radiography
19.
J Rheumatol ; 18(9): 1332-9, 1991 Sep.
Article in English | MEDLINE | ID: mdl-1757934

ABSTRACT

We identified a cohort of 410 patients with connective tissue disorders (CTD) of less than or equal to 1 year duration among the participating clinics of the Cooperative Systematic Studies of the Rheumatic Diseases Program. Fifty-seven had rheumatic arthritis (RA), 57 systemic lupus erythematosus, 37 poly/dermatomyositis, 46 scleroderma, and 213 early undifferentiated CTD, including patients with Raynaud's phenomenon, unexplained polyarthritis or at least 3 CTD manifestations such as rashes, myalgias, etc. Baseline clinical data are now being reported. The followup of these patients may prove to be valuable in understanding these diseases. To our knowledge no similar cohort of patients is available for further investigation.


Subject(s)
Connective Tissue Diseases/epidemiology , Adolescent , Adult , Aged , Arthritis, Rheumatoid/epidemiology , Cohort Studies , Dermatomyositis/epidemiology , Female , Humans , Lupus Erythematosus, Systemic/epidemiology , Male , Middle Aged , Raynaud Disease/epidemiology , Scleroderma, Systemic/epidemiology
20.
J Rheumatol ; 18(9): 1340-3, 1991 Sep.
Article in English | MEDLINE | ID: mdl-1757935

ABSTRACT

The presence of antinuclear antibodies (ANA) in the serum is a common finding in various connective tissue disorders, but usefulness of these antibodies in making diagnoses or prognoses is not known. We report the results of a panel of ANA determinations including ANA, anti-dsDNA, Sm, RNP, SSA, SSB, Jo-1, Scl-70 and PM-1 in 410 patients in a 5-year descriptive study of 410 patients with rheumatic disease symptoms of less than one year's duration. While some patients met diagnostic criteria for a specific rheumatologic diagnosis, others were classified as undifferentiated connective tissue disease (UCTD) and were subclassified by a constellation of symptoms. Our results show that ANA is sensitive in systemic lupus erythematosus (SLE) and progressive systemic sclerosis even in early disease but is not specific. Other "specific" autoantibodies were seen most frequently in SLE but were relatively insensitive and were seen in low frequency in UCTD. ANA have limited diagnostic value in patients with early disease. The prognostic value of these tests will be assessed as the prospective study of these cohorts progresses.


Subject(s)
Antibodies, Antinuclear/analysis , Connective Tissue Diseases/blood , Rheumatic Diseases/blood , Cohort Studies , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/epidemiology , Humans , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/epidemiology , Prognosis , Rheumatic Diseases/diagnosis , Rheumatic Diseases/epidemiology , Scleroderma, Systemic/blood , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/epidemiology , Serologic Tests
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