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Biomedical subjects

John T Sharp

Publications and source records attributed to John T Sharp.

At least 19 recordsLinked to original sources
PubMed2006

Continued inhibition of radiographic progression in patients with psoriatic arthritis following 2 years of treatment with etanercept.

OBJECTIVE: Clinical and radiographic responses were evaluated in patients with psoriatic arthritis (PsA) treated for up to 2 years with etanercept. METHODS: Patients were previously randomized to receive placebo or etanercept in a double-blind study and chose to participate in the current open-label extension phase. All patients received etanercept 25 mg twice weekly. Radiographic progression was determined at baseline, 1 year, and 2 years using the Sharp method modified to include joints frequently affected in PsA. Arthritis and psoriasis responses were determined using American College of Rheumatology 20% (ACR20) improvement criteria, PsA response criteria (PsARC), and the psoriasis area severity index (PASI). RESULTS: Of 205 patients randomized, 169 entered open-label, and 141 [71 randomized to receive placebo (placebo/etanercept) and 70 randomized to receive etanercept (etanercept/etanercept)] had radiographic data available for analysis at 2 years. ACR20 criteria, PsARC, and PASI 50 criteria were met by 64%, 84%, and 62%, respectively, of etanercept/etanercept patients at the end of the 48-week open-label period. Placebo/etanercept patients achieved comparable results within 12 weeks that were sustained at 48 weeks (63%, 80%, and 73%). Radiographic progression was inhibited in the etanercept/ etanercept patients (mean adjusted change in total Sharp score of -0.38 from baseline to 2 yrs). In placebo/etanercept patients, disease progression was inhibited once patients began receiving etanercept (mean adjusted change of -0.22 from 1 year to 2 years). Adverse event rates were similar to those observed during randomized phase, with only one serious adverse event deemed possibly related to etanercept. CONCLUSION: These data demonstrate a sustained benefit of etanercept treatment, including inhibition of radiographic progression, in patients with PsA.

Adolescent↗
PubMed2006

Association of tumor necrosis factor alpha polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort.

OBJECTIVE: To determine whether the tumor necrosis factor alpha (TNFA) -308 guanine-to-adenosine polymorphism and/or the shared epitope (SE) is associated with radiographic damage in patients with early rheumatoid arthritis (RA). METHODS: The cohort consisted of 189 patients with early seropositive RA (median 5.6 months since symptom onset) who had active disease, no previous disease-modifying antirheumatic drug treatment, and >or=2 sets of scored radiographs of the hands/wrists and forefeet. TNFA -308 polymorphism was analyzed by polymerase chain reaction pyrosequencing. The SE was defined as presence of any 1 of the following HLA-DRB1 alleles: *0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001, *1402, or *1406. Radiographic progression was assessed by the total Sharp score. RESULTS: Using a weighted least-squares regression analysis, patients with the -308 TNFA AA plus AG genotypes (n=49) had significantly higher rates of progression in erosion scores (median 0.84 versus 0.48 units/year), joint space narrowing (JSN) scores (0.42 versus 0.04), and total Sharp scores (1.70 versus 0.61) compared with patients with the TNFA GG genotype (n=140). Presence of the SE (n=137) was associated with significantly lower progression rates (per year) for total Sharp scores (median 0.9 versus 1.25 units/year) and JSN scores (0.04 versus 0.41), but not for erosion scores (0.50 versus 0.61) compared with patients without the SE (n=52). In a least-squares multiple linear regression model, the presence of the AA plus AG genotypes was associated with a significantly higher progression rate after adjusting for the presence of the SE, interaction between the SE and the AA plus AG genotypes, baseline log C-reactive protein level, Health Assessment Questionnaire Disability Index, total Sharp score, swollen joint count, and presence of osteophytes (osteoarthritis). There was a strong linkage disequilibrium between DRB1*0301 and TNFA polymorphism (D'=0.84, r2=0.45, P<0.001). CONCLUSION: This study showed an association between the TNFA -308 polymorphism and progression of radiographic damage in patients with early seropositive RA. This association appeared to be independent of the SE, but might be dependent on other genetic variants in linkage disequilibrium with the -308 TNFA A allele and DRB1*0301. Further studies should be conducted to validate these results in both longitudinal observational cohorts and randomized clinical trials.

Arthritis, Rheumatoid↗
PubMed2005

Increased radiographic damage scores at the onset of seropositive rheumatoid arthritis in older patients are associated with osteoarthritis of the hands, but not with more rapid progression of damage.

OBJECTIVE: To investigate the impact of patient age at symptom onset on radiographic joint damage at study entry, and on subsequent progression of damage in a cohort of patients with early seropositive rheumatoid arthritis (RA). METHODS: We studied 186 patients with RA of <15 months' duration. All patients had active disease and had not received disease-modifying antirheumatic drugs. At study entry and during followup, total Sharp scores (TSS), RA-associated joint space narrowing (RA-JSN), and erosions were determined on hand and foot radiographs. Baseline radiographs were also scored for osteoarthritis (OA)-related JSN (OA-JSN) and osteophytes. Older patients (>55 years) and younger patients (</=55 years) were compared by t-test, Mann-Whitney U test, chi-square, or Fisher's exact test. Multiple linear regression models were also constructed. RESULTS: The older group (n = 74) had a higher baseline total Sharp score (median 6.21) compared with the younger group (n = 112) (median 2.33) (P = 0.0002). This was mainly due to a higher baseline JSN score in the older group (median 3.96 versus 1.08) and not to differences in erosion score (median 0.91 versus 0.70). Disease activity and duration of RA symptoms were similar in the 2 groups, as were progression rates of the TSS, JSN score, and erosion score. At baseline, 26% of patients had osteophytes, with a prevalence of 13% in the younger age group and 50% in the older group. The presence of OA-JSN was highly correlated with the presence of osteophytes (r = 0.72). Also, increased age and RA-JSN were associated with increased severity of osteophytes and OA-JSN at baseline. Multiple linear regression analysis showed that both age and hand osteophytes contributed to the increase in baseline RA-JSN score and TSS, but not to erosion score. CONCLUSION: In a cohort of patients with early RA, an increase in the baseline RA-JSN score and TSS can be accounted for in part by the presence of hand OA.

Adult↗
PubMed2005

Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody, was evaluated for its safety and efficacy compared with placebo in the treatment of active psoriatic arthritis (PsA). METHODS: Patients with moderately to severely active PsA and a history of inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks. Study visits were at baseline, weeks 2 and 4, and every 4 weeks thereafter. The primary efficacy end points were the American College of Rheumatology 20% improvement (ACR20) response at week 12 and the change in the modified total Sharp score of structural damage at week 24. Secondary end points were measures of joint disease, disability, and quality of life in all patients, as well as the severity of skin disease in those patients with psoriasis involving at least 3% of body surface area. RESULTS: At week 12, 58% of the adalimumab-treated patients (87 of 151) achieved an ACR20 response, compared with 14% of the placebo-treated patients (23 of 162) (P < 0.001). At week 24, similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was -0.2 in patients receiving adalimumab and 1.0 in those receiving placebo (P < 0.001). Among the 69 adalimumab-treated patients evaluated with the Psoriasis Area and Severity Index (PASI), 59% achieved a 75% PASI improvement response at 24 weeks, compared with 1% of the 69 placebo-treated patients evaluated (P < 0.001). Disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo. Adalimumab was generally safe and well-tolerated. CONCLUSION: Adalimumab significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active PsA.

Adalimumab↗
PubMed2005

Measurement of joint space width and erosion size.

Measurement of radiographic abnormalities in metric units has been reported by several investigators during the last 15 years. Measurement of joint space in large joints has been employed in a few trials to evaluate therapy in osteoarthritis. Measurement of joint space width in small joints has been reported by several investigators but has not yet found a place in clinical trials in rheumatoid arthritis or osteoarthritis. We review methods for measuring joint space width in finger, toe, and wrist joints; special attention is given to how the joint edges are found, the method used to measure distance between joint margins, size of an area of the sampled joint, and reproducibility of measurements. Methods for measurement of erosion size, which have had less attention, are briefly discussed.

Arthrography↗
PubMed2004

Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial.

OBJECTIVE: Tumor necrosis factor (TNF) is an important proinflammatory cytokine that mediates inflammatory synovitis and articular matrix degradation in rheumatoid arthritis (RA). We investigated the ability of adalimumab, a human anti-TNF monoclonal antibody, to inhibit the progression of structural joint damage, reduce the signs and symptoms, and improve physical function in patients with active RA receiving concomitant treatment with methotrexate (MTX). METHODS: In this multicenter, 52-week, double-blind, placebo-controlled study, 619 patients with active RA who had an inadequate response to MTX were randomized to receive adalimumab 40 mg subcutaneously every other week (n = 207), adalimumab 20 mg subcutaneously every week (n = 212), or placebo (n = 200) plus concomitant MTX. The primary efficacy end points were radiographic progression at week 52 (total Sharp score by a modified method [TSS]), clinical response at week 24 (improvements of at least 20% in the American College of Rheumatology core criteria [ACR20]), and physical function at week 52 (disability index of the Health Assessment Questionnaire [HAQ]). RESULTS: At week 52, there was statistically significantly less radiographic progression, as measured by the change in TSS, in the patients receiving adalimumab either 40 mg every other week (mean +/- SD change 0.1 +/- 4.8) or 20 mg weekly (0.8 +/- 4.9) as compared with that in the placebo group (2.7 +/- 6.8) (P < or = 0.001 for each comparison). In addition, there were statistically significant changes in the components of the TSS. At week 24, ACR20 responses were achieved by 63% and 61% of patients in the adalimumab 40 mg every other week and 20 mg weekly groups, respectively, versus 30% of patients in the placebo group (P < or = 0.001 for each comparison). At week 52, ACR20 responses were achieved by 59% and 55% of patients taking adalimumab 40 mg every other week and 20 mg weekly, respectively, versus 24% of patients taking placebo (P < or = 0.001 for each comparison). At week 52, physical function as measured by the HAQ demonstrated statistically significant improvement with adalimumab 40 mg every other week and 20 mg weekly compared with placebo (mean change in HAQ score -0.59 and -0.61, respectively, versus -0.25; P < or = 0.001 for each comparison). A total of 467 patients (75.4%) completed 52 weeks of treatment. Adalimumab was generally well tolerated. Discontinuations occurred in 22.0% of adalimumab-treated patients and in 30.0% of placebo-treated patients. The rate of adverse events (both serious and nonserious) was comparable in the adalimumab and placebo groups, although the proportion of patients reporting serious infections was higher in patients receiving adalimumab (3.8%) than in those receiving placebo (0.5%) (P < or = 0.02), and was highest in the patients receiving 40 mg every other week. CONCLUSION: In this 52-week trial, adalimumab was more effective than placebo at inhibiting the progression of structural joint damage, reducing the signs and symptoms, and improving physical function in patients with active RA who had demonstrated an incomplete response to MTX.

Activities of Daily Living↗
PubMed2004

Classifying structural joint damage in rheumatoid arthritis as progressive or nonprogressive using a composite definition of joint radiographic change: a preliminary proposal.

OBJECTIVE: To categorize radiographic joint damage as progressive or nonprogressive in individuals with rheumatoid arthritis (RA) participating in clinical studies. METHODS: Using the total Sharp radiographic damage score, erosion score, and joint space narrowing (JSN) score for 751 serial films of the hand/wrist and forefoot obtained from 190 patients with early RA during 6-60 months of followup (mean 31 months), various threshold values for progression of joint damage were evaluated singly and in various combinations. For each patient, the progression rate was estimated from the linear regression line for all available radiographic time points. After preliminary screening, 23 candidate definitions were tested to select a definition that discriminated well between radiographic progression and radiographic nonprogression. RESULTS: The definition selected describes radiographic nonprogression in individual patients as an increase of < or =0.1 in the standardized response mean of the trimmed population (the central 95% of patients) for > or =5 of 6 change measures (erosion scores and JSN scores for the fingers, wrists, and feet). Using this definition, 59% of the 190 patients with early RA were defined as having nonprogressive radiographic damage. Moreover, 95% of 95 patients with progression of the total Sharp score at or below the median and 24% of 95 patients with progression of the total Sharp score above the median were defined as having nonprogressive joint damage (chi(2) = 98, P < 0.0001), as were 97% of patients in the lowest quintile of total Sharp score progression rates and none of the patients in the highest progression quintile. Patients defined as nonprogressors had significantly lower baseline levels of C-reactive protein and lower erythrocyte sedimentation rates compared with patients defined as progressors, and those patients in the nonprogressive joint damage group more frequently had American College of Rheumatology 20% and 50% improvement criteria responses, "good" improvements (decrease of > or =1.2) in the Disease Activity Score, and > or =50% decreases in the swollen joint counts during the first 2 years of followup. CONCLUSION: RA joint damage in an observational cohort can be classified as progressive or nonprogressive with the use of a composite definition. Validation and/or refinement of this definition is needed by utilizing the data from controlled clinical trials that compare placebo with active treatment.

Antirheumatic Agents↗
PubMed2004

Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression.

OBJECTIVE: Etanercept has been shown to improve the articular and cutaneous manifestations of psoriatic arthritis (PsA). In this study, we further evaluated the safety, efficacy, and effect on radiographic progression of etanercept in patients with PsA. METHODS: Patients with PsA (n = 205) were randomized to receive placebo or 25 mg etanercept subcutaneously twice weekly for 24 weeks. Patients continued to receive blind-labeled therapy in a maintenance phase until all had completed the 24-week phase, then could receive open-label etanercept in a 48-week extension. Efficacy and safety were evaluated at 4, 12, and 24 weeks and at 12-week intervals thereafter. Radiographs of the hands and wrists were assessed at baseline and 24 weeks, at entry to the open-label phase, and after 48 weeks in the study. RESULTS: Etanercept significantly reduced the signs and symptoms of PsA and psoriasis. At 12 weeks, 59% of etanercept patients met the American College of Rheumatology 20% improvement criteria for joint response, compared with 15% of placebo patients (P < 0.0001), and results were sustained at 24 and 48 weeks. At 24 weeks, 23% of etanercept patients eligible for psoriasis evaluation achieved at least 75% improvement in the Psoriasis Area and Severity Index, compared with 3% of placebo patients (P = 0.001). Radiographic disease progression was inhibited in the etanercept group at 12 months; the mean annualized rate of change in the modified total Sharp score was -0.03 unit, compared with +1.00 unit in the placebo group (P = 0.0001). Etanercept was well tolerated. CONCLUSION: Etanercept reduced joint symptoms, improved psoriatic lesions, inhibited radiographic progression, and was well tolerated in patients with PsA.

Adult↗
PubMed2004

Measurement of structural abnormalities in arthritis using radiographic images.

This article reviewed the current methods for scoring radiographic abnormalities in RA with emphasis on reliability. There is disagreement on the expected course of RA with usual treatment and there is no clear resolution of this disagreement although several factors that contribute to this disagreement have been identified. Scoring joint damage has been effective in establishing benefit from drug treatment for nine agents, five within the last 3 years. Scoring will continue to be used to examine the benefit of new agents in the immediate years to come. A panel of experienced readers agreed that some repair of erosion damage was seen with available treatment. The extent of damage that is reversible has not been established and the frequency of any degree of repair remains unknown. Several methods of true measurement of erosions and joint space width have been reported. They have not found a place in daily practice or in research studies, probably because experience is too limited to know whether they are more powerful in detecting real progression of disease than scoring methods. Several problems that are related to standardizing methods of measuring joint space width were identified.

Adrenal Cortex Hormones↗
PubMed2004

Patient retention and hand-wrist radiograph progression of rheumatoid arthritis during a 3-year prospective study that prohibited disease modifying antirheumatic drugs.

OBJECTIVE: To quantitate patient retention and radiographic progression rates in serial hand/wrist radiographs of patients with rheumatoid arthritis (RA) who were not being treated with disease modifying antirheumatic drugs (DMARD). METHODS: A total of 1433 RA patients with 1-7 years' disease duration entered a 3-year prospective randomized double-blind clinical trial comparing the nonsteroidal antiinflammatory drugs (NSAID) etodolac (300 or 1000 mg daily) and ibuprofen (2400 mg daily). Standardized hand/wrist radiographs were obtained yearly and at dropout if > 6 months after entry. DMARD were not permitted. Joint erosion, joint space narrowing (JSN), and total scores of 3 readers were averaged. RESULTS: At entry, mean duration of RA was 3.5 years (range 1-7); ages were 21-78 years; patients were 71% female, 84% Caucasian, 67% rheumatoid factor (RF) positive; tender joint count was 29, swollen joint count 22, Westergren erythrocyte sedimentation rate (ESR) 49, and C-reactive protein (CRP) 2.44. There were 824 (57.5%) patients who completed >or= 6 months and had paired radiographs; 46% completed 48 weeks; 31%, 98 weeks; and 19%, 147 weeks. Months between paired radiographs (time in study) averaged 23.1 (range 6-36). Mean progression rates for total, erosion, and JSN scores (5.08, 2.53, and 2.54 units per year, respectively) were significantly associated with time in study, baseline RF, ESR, CRP, swollen joint count, presence of erosions at entry, and with 20% and 50% composite clinical responses. Painful joint count and RA duration were weakly associated only with progression of erosions. Progression rates were not associated with age, sex, corticosteroid use, or prior DMARD use. Patients who completed the 3-year trial had less severe disease activity and radiographic progression than those who dropped out. CONCLUSION: In this 3-year prospective double-blind clinical trial that prohibited DMARD, retention rates (57.5%, 46%, 31%, and 19% at 0.5, 1, 2, and 3 years) were similar to those in the non-DMARD-treated placebo groups of recent published studies. Radiographic progression rates are reported for 824 non-DMARD-treated patients during RA of 1-10 years' duration. This information may be useful as background information in the interpretation of longterm clinical trials that evaluate joint radiographic outcomes.

Adult↗
PubMed2004

Variability of precision in scoring radiographic abnormalities in rheumatoid arthritis by experienced readers.

OBJECTIVE: To determine the extent of precision and sources of variability among experts on scoring radiographic abnormalities in rheumatoid arthritis. METHODS: Radiographic scores from 6 datasets in which 2 or more readers had scored film sets were analyzed. Datasets included scores by 11 different readers, 6 of whom scored films by both the Larsen (global) and Sharp (composite) methods. Scores of each possible combination of 2 readers were compared in calculating the smallest detectable difference (SDD) on raw scores and on scores normalized for each individual reader (nSDD). Intraclass correlation (ICC), Pearson's r, and the correlation between differences in score and their mean scores were determined. Agreement on progression of radiographic damage scores was also examined. RESULTS: Variability among readers was greater than previous studies suggested. Agreement was better for intra- than interreader comparisons; average intrareader SDD was 24.4 for the composite method and 9.0 for the global. The larger SDD for the composite method reflect their greater range of possible scores. When normalized scores were used to adjust for the range difference, there was minimal difference in the SDD; nSDD was 10.1 for the composite method, 8.0 for the global. Interreader variability was larger: SDD of 53.7 for the composite method and 23.3 for the global; nSDD 12.9 and 14.4, respectively. ICC varied between 0.465 and 0.999, with all but one value below 0.925 occurring in composite scores with a range below 100. Differences in repeated scores were frequently associated with the mean of those scores and this was greater for inter- than for intrareader comparisons. Agreement between progression scores showed a similar pattern. The SDD was better for intrareader comparisons and smaller for global scores: compare 13.7 (composite, intrareader) and 5.4 (global, intrareader) to 18.1 (composite, interreader) and 8.7 (global, interreader). The ICC was lower for progression scores than for raw scores, averaging between 0.661 and 0.885. CONCLUSION: The variability in scoring radiographic abnormalities is considerable among this group of 11 expert readers. This has important implications for power calculations in comparison studies such as therapeutic trials and for cross-trial comparisons. The correlation between the difference in repeated scores and their means indicates systematic error (bias), which, if corrected, may improve the detection of treatment effects when using a responder-type analysis. These and other design and analysis issues are discussed.

Arthritis, Rheumatoid↗
PubMed2003

Correlation of single time-point damage scores with observed progression of radiographic damage during the first 6 years of rheumatoid arthritis.

OBJECTIVE: Aggressive treatment of early rheumatoid arthritis (RA) is recommended to prevent irreversible joint damage. We evaluated the usefulness of single time-point joint radiographs for deciding whether early RA is erosive or nonerosive. METHODS: In an observational study, 179 patients with recent onset of RA symptoms (median 5.1 mo), positive rheumatoid factor, and active polyarthritis had 2 to 8 radiographic observations of hands, wrists, and forefeet during 6 to 60 months of followup. Linear regression lines for all available radiographs were used to determine progression rates of total Sharp score (TSS), erosion score (ES), and joint space narrowing score (JSNS) of each patient. RESULTS: Using the average of 2 readers' scores, intraclass correlation coefficient was 0.97 and smallest detectable difference was 3.07 for ES, 0.93 and 7.52 for JSNS, and 0.90 and 12.71 for TSS. Mean progression rates per year were 1.20 (ES), 0.67 (JSNS), and 1.85 (TSS). Single time-point radiographs taken within 6 months of symptom onset did not correlate with progression rates (r = 0.01 to 0.07); between 7 and 18 months correlations were weak (r = 0.23 to 0.35), but were better for ES between 19 and 72 months (r = 0.60 to 0.81). Among 53 patients (31%) with no progression of TSS, only 10 of them had zero scores at baseline. Among all 630 radiographs with TSS > or = 1, 25% were associated with progression rates < or = 0. CONCLUSION: Erosion scores of single radiographic examinations done > 18 months after onset of RA symptoms correlated with progression rates, but earlier radiographs did not sufficiently predict erosive or nonerosive status to guide disease modifying antirheumatic drug treatment decisions.

Adult↗
PubMed2003

Repair of erosions in rheumatoid arthritis does occur. Results from 2 studies by the OMERACT Subcommittee on Healing of Erosions.

The committee was charged with determining whether healing of erosions in rheumatoid arthritis (RA) occurs. Two exercises were performed: The first asked the committee members, as a panel of experts, to express agreement or disagreement with the presence of improvement and features of bone reaction to injury in images submitted by members as examples of healing. The second presented panel members with 28 pairs of serial images, 14 chosen to illustrate progression and 14 chosen to illustrate repair. Agreement was tested on 8 items: global judgment on which image in the pair was better, relative size of the erosion in the 2 images, judgment on which image was first, presence and extent of sclerosis, cortication, filling-in, remodeling, and reconstituting normal structure. Our results showed good agreement, among the 15 respondents, on global assessment of which image was better and which image showed the smaller erosion. Correct assignment of sequence was only slightly better than expected by chance (in 65% of the cases). Agreement was poor regarding the presence of morphologic features of bone repair. A majority of a panel of experts agreed on which 2nd images in a set of paired, serial images represented improvement and which showed progression based on global assessment of which was better and on size of erosion. Features of bone repair were not distinctive and did not enable the panel to deduce the correct sequence of the serial images. This study provides evidence that repair of bone damage in RA does occur, resulting in some degree of improvement, which was recognized by a majority of a panel of experts.

Arthritis, Rheumatoid↗
PubMed2002

A 12-month, multicenter, prospective, open-label trial of radiographic analysis of disease progression in osteoarthritis of the knee or hip in patients receiving celecoxib.

BACKGROUND: Studies have suggested that nonspecific nonsteroidal anti-inflammatory drugs may inhibit matrix biosynthesis by articular cartilage, thereby accelerating the progression of osteoarthritis (OA). OBJECTIVE: The objective of this analysis was to determine whether 1-year treatment with the cyclooxygenase-2-specific inhibitor celecoxib at up to twice the recommended and maximally effective dose for OA had any deleterious effects on OA progression by assessing radiographic changes in knee or hip joint morphology in patients with OA. METHODS: In a 12-month, multicenter, prospective, open-label trial, patients with OA of the knee or hip or rheumatoid arthritis received celecoxib at doses ranging from that recommended for the treatment of OA (200 mg/d) to twice the recommended daily dosage (400 mg/d). Available radiographs showing baseline and end-of-treatment status were analyzed using semiquantitative measures of index joint morphology in patients with mild to moderate OA. The morphologic scores were then subjected to mean change and shift-table analysis to determine the extent and rate of disease progression. RESULTS: A total of 2,327 patients (796 with OA of the knee, 1,531 with OA of the hip) were included. A subset of 344 patients (160 with OA of the knee, 184 with OA of the hip) had radiographs from both before and after 12 months' celecoxib treatment. One hundred forty-seven and 158 pairs of knee and hip radiographs, respectively, were available for analysis. These revealed that, with the exception of significant hip joint-space narrowing (P = 0.029), no evidence of disease progression with long-term celecoxib treatment could be detected. The observed increase in hip joint-space narrowing was small (0.14 units/y) (95% CI, 0.08-0.20), was observed prior to celecoxib exposure (by mean change or shift-table analysis), and was not dose related. CONCLUSION: These results are consistent with the hypothesis that long-term therapy with celecoxib does not accelerate progression of OA of the knee or hip.

Adult↗