Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: results of a fifty-two-week, randomized, controlled study

OBJECTIVE: To assess the efficacy, safety, and tolerability of etoricoxib, a cyclooxygenase 2 (COX-2) selective inhibitor, administered continuously over 52 weeks for the treatment of ankylosing spondylitis (AS). METHODS: This 2-part, multicenter, double-blind, parallel-group, 52-week study evaluated 2 doses of etoricoxib (90 and 120 mg) compared with naproxen at 1,000 mg. A 6-week, active-comparator- and placebo-controlled period (part I) was followed by a 46-week active-comparator-controlled period (part II). The primary outcome measures (on 100-mm visual analog scales) were patient's assessment of spine pain, patient's global assessment of disease activity, and the Bath Ankylosing Spondylitis Functional Index. RESULTS: Of the 387 patients randomized to receive treatment, 301 (77.8%) completed part I and 284 (75.9%) completed part II. Compared with placebo over 6 weeks, those receiving 90 mg etoricoxib, 120 mg etoricoxib, and naproxen demonstrated significantly (P < 0.001) greater improvement in all primary end points; treatment effects (expressed as the difference in least squares mean change versus placebo) were 21-29 mm for spine pain, 18-25 mm for disease activity, and 11-15 mm for function. Compared with patients receiving naproxen, significantly greater improvement in all primary end points was demonstrated in the combined group receiving either 90 mg etoricoxib or 120 mg etoricoxib over 6 weeks, in each individual etoricoxib treatment group over 6 weeks, and in the combined etoricoxib group over 1 year (all P < 0.05); results for secondary and exploratory end points were generally consistent with those from the primary analysis. Among all groups, there were no significant differences in the incidence of overall clinical, drug-related, or serious adverse experiences (AEs) and discontinuations due to AEs. Safety observations during part II were generally consistent with those in part I. CONCLUSION: Etoricoxib at doses of 90 mg and 120 mg demonstrated superior efficacy compared with placebo over 6 weeks, and compared with naproxen over 1 year. These study results demonstrate that etoricoxib is generally safe, well-tolerated, and efficacious for the treatment of AS.     

Efficacy and safety of adalimumab in patients with ankylosing spondylitis: Results of a multicenter,randomized, double‐blind,placebo‐controlled trial

Objective

To evaluate the safety and efficacy of adalimumab, a fully human recombinant IgG1 monoclonal antibody that specifically targets human tumor necrosis factor, in patients with active ankylosing spondylitis (AS).

Methods

This was a multicenter, randomized (2:1 ratio), double‐blind, placebo‐controlled study to evaluate a subcutaneous injection of adalimumab, 40 mg every other week, compared with placebo for 24 weeks. The primary efficacy end point was the percentage of patients with a 20% response according to the ASsessment in Ankylosing Spondylitis International Working Group criteria for improvement (ASAS20) at week 12. Secondary outcome measures included the ASAS20 at week 24 and multiple measures of disease activity, spinal mobility, and function, as well as ASAS partial remission.

Results

At week 12, 58.2% of adalimumab‐treated patients (121 of 208) achieved an ASAS20 response, compared with 20.6% of placebo‐treated patients (22 of 107) (P < 0.001). More patients in the adalimumab group (45.2% [94 of 208]) than in the placebo group (15.9% [17 of 107]) had at least a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index at week 12 (P < 0.001). Significant improvements in the ASAS40 response and the response according to the ASAS5/6 criteria at weeks 12 and 24 were also demonstrated (P < 0.001). Partial remission was achieved by more adalimumab‐treated patients than placebo‐treated patients (22.1% versus 5.6%; P < 0.001). Adalimumab‐treated patients reported more adverse events (75.0% versus 59.8% of placebo‐treated patients; P < 0.05), but there was no statistically significant difference in the incidence of infections. Most adverse events were mild or moderate in severity.

Conclusion

Adalimumab was well‐tolerated during the 24‐week study period and was associated with a significant and sustained reduction in the signs and symptoms of active AS.

     

Evaluation of the efficacy and safety of terguride in patients with fibromyalgia syndrome: Results of a twelve‐week,multicenter, randomized,double‐blind,placebo‐controlled,parallel‐group study

Objective

To assess the efficacy and safety of terguride, a partial dopamine agonist, in patients with fibromyalgia syndrome (FMS).

Methods

In a 12‐week, multicenter, double‐blind, placebo‐controlled, parallel‐group study, 99 patients were randomized at a ratio of 2 to 1 to receive terguride or placebo. Over 21 days, the dosage was titrated to a maximum daily dose of 3 mg of terguride or placebo, and this fixed dosage was continued over 9 weeks. The primary efficacy variable was the intensity of pain (100‐mm visual analog scale). Secondary efficacy variables included the Fibromyalgia Impact Questionnaire (FIQ) score, the tender point score (TPS), and the Hamilton Depression Scale (HDS) score. During the study, patients were evaluated for the presence of cervical spine stenosis by magnetic resonance imaging (MRI).

Results

No significant differences in the change in pain intensity, FIQ score, TPS, or HDS score between baseline and 12 weeks were observed in the terguride group as compared with the placebo group. Cervical spine stenosis was detected in 22% of the patients. Only patients with cervical spine stenosis responded to terguride treatment. FIQ scores improved significantly (per‐protocol analysis), and pain intensity, the TPS score, and the HDS score showed a trend toward improvement in the terguride group as compared with the placebo group. Terguride treatment was safe. Only those adverse events already known to be side effects of terguride were observed. Premature termination of the study in patients receiving terguride (26%) occurred predominantly during up‐titration and in the absence of comedication for treatment of nausea.

Conclusion

Terguride treatment did not improve pain, the FIQ score, the TPS, or the HDS score in the total study population. However, a subgroup of patients with cervical spine stenosis seemed to benefit from terguride treatment.

     

Health‐related quality of life outcomes in patients with active ankylosing spondylitis treated with adalimumab: Results from a randomized controlled study

Objective

To evaluate the impact of adalimumab on health‐related quality of life (HRQOL) in patients with active ankylosing spondylitis (AS).

Methods

Patients ≥18 years enrolled in the Adalimumab Trial Evaluating Long‐Term Efficacy and Safety in Ankylosing Spondylitis, a randomized controlled study, were randomly assigned to receive either adalimumab 40 mg subcutaneously or placebo every other week for 24 weeks. ASsessment of Ankylosing Spondylitis (ASAS) International Working Group criteria were used to evaluate clinical efficacy. HRQOL outcomes were assessed using the Short Form 36 (SF‐36) Health Survey and Ankylosing Spondylitis Quality of Life (ASQoL) Questionnaire.

Results

A total of 315 patients enrolled (208 in the adalimumab group and 107 in the placebo group). Patients in the adalimumab group showed significant improvements in SF‐36 Physical Component Summary (PCS) and ASQoL scores versus placebo at weeks 12 and 24 (P < 0.001). The observed differences between adalimumab and placebo patients exceeded the a priori minimum important difference (MID) at the group level, and significantly more adalimumab‐treated patients achieved improvements greater than the MID on the patient level. These data suggest the HRQOL improvements were clinically meaningful. No differences were observed in SF‐36 Mental Component Summary (MCS) scores. Significant differences favoring adalimumab were observed for SF‐36 domains physical function, bodily pain, role‐physical, general health, vitality, social function, and role–emotional. There was significant association between HRQOL improvements (measured by SF‐36 PCS and MCS, and ASQoL scores) and ASAS clinical responses (P < 0.001).

Conclusion

Adalimumab significantly improved physical health status and overall HRQOL through 24 weeks in patients with active AS.     

Infliximab improves productivity and reduces workday loss in patients with ankylosing spondylitis: Results from a randomized,placebo‐controlled trial

Objective

To examine whether clinical benefits observed after treatment with infliximab were accompanied by improvement in productivity and reduction in time lost from work in a randomized, double‐blind, placebo‐controlled, multicenter trial of patients with ankylosing spondylitis (AS).

Methods

Adults with active AS receiving standard antiinflammatory treatment were randomly assigned in a 3:8 ratio to receive infusions of placebo or 5 mg/kg infliximab at weeks 0, 2, 6, and every 6 weeks thereafter through week 24. Physical function was measured using the Bath Ankylosing Spondylitis Functional Index. The impact of disease on productivity was measured using a visual analog scale (range 0–10). Self‐reported employment status and time lost at work before and during the trial were collected. Spearman's correlation coefficient was used to examine factors associated with productivity.

Results

Patients treated with infliximab had a more significant reduction in limitations of work and daily activity due to physical or emotional problems than patients treated with placebo. Of the subset of patients employed full time, patients in the infliximab group had a significantly greater improvement in productivity as early as week 6 compared with the placebo group. The median change from baseline in the productivity score at week 24 was 0.7 (median percent change 11%) in the placebo group compared with 2.1 (62%) in the infliximab group (P < 0.05). Daily productivity was significantly correlated with physical function and disease activity at baseline and week 24.

Conclusion

The daily productivity of patients with active AS was significantly associated with functional impairment and disease activity. Infliximab treatment significantly improved productivity and reduced workday loss among employed patients with AS.

     

Efficacy and safety of infliximab in patients with ankylosing spondylitis: Results of a randomized,placebo‐controlled trial (ASSERT)

Objective

The signs and symptoms of ankylosing spondylitis (AS) respond inadequately to nonsteroidal antiinflammatory drugs, corticosteroids, and disease‐modifying antirheumatic drugs in quite a number of patients. Tumor necrosis factor inhibitors have demonstrated success in reducing AS disease activity in a limited number of clinical trials. The objective of this multicenter, randomized, placebo‐controlled study was to evaluate the efficacy and safety of infliximab in patients with AS.

Methods

Patients were randomly assigned to receive infusions of placebo or 5 mg/kg infliximab at weeks 0, 2, 6, 12, and 18. Efficacy was assessed using the ASsessment in Ankylosing Spondylitis (ASAS) International Working Group criteria, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), night pain, patient's global assessment, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), chest expansion, the Mander enthesis index, the total swollen joint index, the C‐reactive protein level, and the Short Form 36 (SF‐36) health survey questionnaire. The primary end point in this study was the proportion of patients with a 20% improvement response according to the ASAS International Working Group criteria (ASAS20 responders) at week 24.

Results

Of the 357 patients screened, 201 were assigned to receive 5 mg/kg infliximab and 78 were assigned to receive placebo. After 24 weeks, 61.2% of patients in the infliximab group were ASAS20 responders compared with 19.2% of patients in the placebo group (P < 0.001). Clinical benefit was observed in patients receiving infliximab as early as week 2 and was maintained over the 24‐week study period. Patients receiving infliximab also showed significant improvements in the BASDAI, BASFI, BASMI, chest expansion, and physical component summary score of the SF‐36. Adverse events were reported by 82.2% of patients receiving infliximab and by 72.0% of patients receiving placebo; however, most adverse events in both treatment groups were mild or moderate in severity.

Conclusion

Infliximab was well tolerated and effective in a large cohort of patients with AS during a 24‐week study period.

     

Long‐term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: An open,observational, extension study of a three‐month,randomized, placebo‐controlled trial

Objective

Treatment of ankylosing spondylitis (AS) with infliximab, an anti–tumor necrosis factor α monoclonal antibody, was shown to be efficacious in patients with active disease during a 3‐month treatment period. The purpose of this study was to evaluate the efficacy and safety of infliximab treatment of AS for a 1‐year period.

Methods

This study was an open, observational, extension study of a 3‐month, randomized, placebo‐controlled trial. All patients who had tolerated infliximab (infliximab/infliximab group) or placebo (placebo/infliximab 12‐week crossover group) therapy for 3 months entered the open extension trial (n = 65). Infliximab was administered at a dosage of 5 mg/kg every 6 weeks after the induction phase (weeks 0, 2, and 6). The primary end point was a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).

Results

At week 54, a total of 54 of the 69 patients (78%) continued to take infliximab. The intent‐to‐treat primary efficacy analysis at week 54 showed that 47% of patients in the infliximab/infliximab group (95% confidence interval 31–63) and 51% of the patients in the placebo/infliximab group (95% confidence interval 36–67) achieved 50% improvement in BASDAI scores. In the analysis of those who completed the study, the mean BASDAI scores improved between weeks 0 and 54 in both treatment groups: from 6.6 to 2.4 in the infliximab/infliximab group and from 6.3 to 2.6 in the placebo/infliximab group. The dosage of nonsteroidal antiinflammatory drugs was reduced in ∼70% of the patients. There were significant improvements in measures of functioning, metrologic parameters, and quality of life. Between weeks 12 and 54, a total of 4 patients had serious adverse events that were possibly related to infliximab and resulted in their discontinuing the study.

Conclusion

Infliximab therapy in AS patients resulted in a rapid and significant improvement in BASDAI scores (>50% improvement) and a durable response for 1 year. The safety profile of infliximab in AS was comparable to that observed in the postmarketing experience for the approved indications.

     

Combined spa–exercise therapy is effective in patients with ankylosing spondylitis: a randomized controlled trial

Objective

To determine the efficacy of combined spa–exercise therapy in addition to standard treatment with drugs and weekly group physical therapy in patients with ankylosing spondylitis (AS).

Methods

A total of 120 Dutch outpatients with AS were randomly allocated into 3 groups of 40 patients each. Group 1 (mean age 48 ± 10 years; male:female ratio 25:15) was treated in a spa resort in Bad Hofgastein, Austria; group 2 (mean age 49 ± 9 years; male:female ratio 28:12) in a spa resort in Arcen, The Netherlands. The control group (mean age 48 ± 10 years; male:female ratio 34:6) stayed at home and continued their usual drug treatment and weekly group physical therapy during the intervention weeks. Standardized spa–exercise therapy of 3 weeks duration consisted of group physical exercises, walking, correction therapy (lying supine on a bed), hydrotherapy, sports, and visits to either the Gasteiner Heilstollen (Austria) or sauna (Netherlands). After spa–exercise therapy all patients followed weekly group physical therapy for another 37 weeks. Primary outcomes were functional ability, patient's global well‐being, pain, and duration of morning stiffness, aggregated in a pooled index of change (PIC).

Results

Analysis of variance showed a statistically significant time–effect (P < 0.001) and time‐by‐treatment interaction (P = 0.004), indicating that the 3 groups differed over time with respect to the course of the PIC. Four weeks after start of spa–exercise therapy, the mean difference in PIC between group 1 and controls was 0.49 (95% confidence interval [CI] 0.16–0.82, P = 0.004) and between group 2 and controls was 0.46 (95% CI 0.15–0.78, P = 0.005). At 16 weeks, the difference between group 1 and controls was 0.63 (95% CI 0.23–1.02, P = 0.002) and between group 2 and controls was 0.34 (95% CI − 0.05–0.73; P = 0.086). At 28 and 40 weeks, more improvement was found for group 1 compared with controls (P = 0.012 and P = 0.062, respectively) but not for group 2 compared with controls.

Conclusion

In patients with AS, a 3‐week course of combined spa–exercise therapy, in addition to drug treatment and weekly group physical therapy alone, provides beneficial effects. These beneficial effects may last for at least 40 weeks.

     

Maintenance of infliximab treatment in ankylosing spondylitis: Results of a one‐year randomized controlled trial comparing systematic versus on‐demand treatment

Objective

Continuous treatment with the anti–tumor necrosis factor α (anti‐TNFα) antibody infliximab is efficacious in ankylosing spondylitis (AS), whereas treatment discontinuation results in disease relapse, with variable delay. This study was undertaken to compare the efficacy of continuous treatment with infliximab with that of a treatment regimen adapted to symptom recurrence. Methotrexate (MTX) in combination with infliximab was also tested.

Methods

Patients with active AS were randomly assigned at week 0 to receive infliximab every 6 weeks (continuous treatment) or upon symptom recurrence (on‐demand treatment), following infusions at weeks 4, 6, and 10. Patients in the on‐demand group were randomly assigned to receive either MTX in combination with infliximab or infliximab alone. Patients were monitored for 1 year. The primary end point was the proportion of patients who met the ASsessment in AS International Working Group criteria for 20% improvement (ASAS20) at week 58.

Results

Of 247 patients, 124 were assigned to receive infliximab every 6 weeks and 123 to receive on‐demand treatment. Among the latter, 62 received MTX, and 61 received infliximab alone. A greater proportion of patients receiving infliximab every 6 weeks fulfilled ASAS20 response criteria at week 58 than did patients receiving on‐demand treatment (75% versus 46%; P < 0.0001). Patients in the continuous treatment group received more infliximab infusions after week 10 than did those in the on‐demand group (mean ± SD 5.8 ± 2.2 versus 3.5 ± 2; P < 0.0001). Addition of MTX did not significantly affect the proportion of patients with an ASAS20 response at week 58, nor the number of infliximab infusions administered.

Conclusion

These findings indicate that continuous treatment of AS with infliximab is more efficacious than on‐demand treatment, and that the addition of MTX to infliximab provides no significant benefit.

     

Cost effectiveness of combined spa–exercise therapy in ankylosing spondylitis: A randomized controlled trial

Objective

To evaluate the cost effectiveness and cost utility of a 3‐week course of combined spa therapy and exercise therapy in addition to standard treatment consisting of antiinflammatory drugs and weekly group physical therapy in ankylosing spondylitis (AS) patients.

Methods

A total of 120 Dutch outpatients with AS were randomly allocated into 3 groups of 40 patients each. Group 1 was treated in a spa resort in Bad Hofgastein, Austria; group 2 in a spa resort in Arcen, The Netherlands. The control group stayed at home and continued their usual activities and standard treatment during the intervention weeks. After the intervention, all patients followed weekly group physical therapy. The total study period was 40 weeks. Effectiveness of the intervention was assessed by functional ability using the Bath Ankylosing Spondylitis Function Index (BASFI). Utilities were measured with the EuroQoL (EQ‐5D_utility). A time‐integrated summary score defined the clinical effects (BASFI‐area under the curve [AUC]) and utilities (EQ‐5D_utility‐AUC) over time. Both direct (health care and non‐health care) and indirect costs were included. Resource utilization and absence from work were registered weekly by the patients in a diary. All costs were calculated from a societal perspective.

Results

A total of 111 patients completed the diary. The between‐group difference for the BASFI‐AUC was 1.0 (95% confidence interval [95% CI] 0.4–1.6; P = 0.001) for group 1 versus controls, and 0.6 (95% CI 0.1–1.1; P = 0.020) for group 2 versus controls. The between‐group difference for EQ‐5D_utility‐AUC was 0.17 (95% CI 0.09–0.25; P < 0.001) for group 1 versus controls, and 0.08 (95% CI 0.00–0.15; P = 0.04) for group 2 versus controls. The mean total costs per patient (including costs for spa therapy) in Euros (€) during the study period were €3,023 for group 1, €3,240 for group 2, and €1,754 for the control group. The incremental cost‐effectiveness ratio per unit effect gained in functional ability (0–10 scale) was €1,269 (95% CI 497–3,316) for group 1, and €2,477 (95% CI 601–12,098) for group 2. The costs per quality‐adjusted life year gained were €7,465 (95% CI 3,294–14,686) for group 1, and €18,575 (95% CI 3,678–114,257) for group 2.

Conclusion

Combined spa–exercise therapy besides standard treatment with drugs and weekly group physical therapy is more effective and shows favorable cost‐effectiveness and cost‐utility ratios compared with standard treatment alone in patients with AS.

     

Major reduction in spinal inflammation in patients with ankylosing spondylitis after treatment with infliximab: Results of a multicenter,randomized, double‐blind,placebo‐controlled magnetic resonance imaging study

Objective

To determine whether the effects of anti–tumor necrosis factor α (TNFα) in reducing the signs and symptoms of ankylosing spondylitis (AS) coincide with a reduction in spinal inflammation as detected by magnetic resonance imaging (MRI).

Methods

Pre‐ and postgadolinium T1 and STIR MR images of the spine were acquired at baseline and at week 24 in patients with AS who participated in a multicenter, randomized, double‐blind, placebo‐controlled study. Patients were randomly assigned at an 8:3 ratio to receive infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, and 6 and then every 6 weeks thereafter. MR images were obtained and evaluated independently by 2 readers who were blinded to the treatment allocation and time sequence of the images.

Results

A total of 194 patients in the infliximab group and 72 patients in the placebo group had evaluable images at baseline and week 24. About 80% of the patients had at least 1 active spinal lesion at baseline, as assessed by MRI. The improvement in the MRI Activity Score after 6 months was significantly greater in the patients who received infliximab (mean 5.02, median 2.72) than in those who received placebo (mean 0.60, median 0.0) (P < 0.001). Almost complete resolution of spinal inflammation was seen in most patients who received infliximab, irrespective of baseline activity.

Conclusion

Patients with AS who received infliximab therapy showed a decrease in spinal inflammation as detected by MRI, whereas those who received placebo showed persistent inflammatory spondylitis.

     

Effect of aquatic exercise on ankylosing spondylitis: a randomized controlled trial

Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease that affects mainly the axial skeleton and causes significant pain and disability. Aquatic (water-based) exercise may have a beneficial effect in various musculoskeletal conditions. The aim of this study was to compare the effectiveness of aquatic exercise interventions with land-based exercises (home-based exercise) in the treatment of AS. Patients with AS were randomly assigned to receive either home-based exercise or aquatic exercise treatment protocol. Home-based exercise program was demonstrated by a physiotherapist on one occasion and then, exercise manual booklet was given to all patients in this group. Aquatic exercise program consisted of 20 sessions, 5× per week for 4 weeks in a swimming pool at 32–33 °C. All the patients in both groups were assessed for pain, spinal mobility, disease activity, disability, and quality of life. Evaluations were performed before treatment (week 0) and after treatment (week 4 and week 12). The baseline and mean values of the percentage changes calculated for both groups were compared using independent sample t test. Paired t test was used for comparison of pre- and posttreatment values within groups. A total of 69 patients with AS were included in this study. We observed significant improvements for all parameters [pain score (VAS) visual analog scale, lumbar flexion/extension, modified Schober test, chest expansion, bath AS functional index, bath AS metrology index, bath AS disease activity index, and short form-36 (SF-36)] in both groups after treatment at week 4 and week 12 (p < 0.05). Comparison of the percentage changes of parameters both at week 4 and week 12 relative to pretreatment values showed that improvement in VAS (p < 0.001) and bodily pain (p < 0.001), general health (p < 0.001), vitality (p < 0.001), social functioning (p < 0.001), role limitations due to emotional problems (p < 0.001), and general mental health (p < 0.001) subparts of SF-36 were better in aquatic exercise group. It is concluded that a water-based exercises produced better improvement in pain score and quality of life of the patients with AS compared with home-based exercise.     

Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial

OBJECTIVE: To evaluate the efficacy and safety of methotrexate (MTX) compared with placebo in patients with active ankylosing spondylitis (AS). METHODS: This 24 week, double bind, randomized, placebo controlled trial compared the response between MTX 7.5 mg/week or placebo in patients with active AS. The primary outcome measure was a composite index of improvement in 5 of the following scales: severity of morning stiffness, physical well being, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S), and physician and patient global assessment of disease activity. RESULTS: Seventeen patients received MTX and 18 placebo. In the intention-to-treat analysis at 24 weeks, 53% of patients in the MTX group had a treatment response, compared with 17% in the placebo group (p = 0.03). We observed significant improvements with MTX in physical well being (p = 0.009), BASDAI (p = 0.02), BASFI (p = 0.02), physician global assessment (p < 0.001), patient global assessment (p = 0.03), and HAQ-S (p = 0.02). In the adjusted analysis only MTX determined the improvement in the primary outcome. At the end of the trial, one patient with MTX withdrew due to a lack of compliance, and one with placebo due to a lack of efficacy. We did not observe significant differences in rates of side effects between the 2 groups. CONCLUSION: MTX is safe and effective for patients with AS. Longterm studies are needed to evaluate the permanence of its benefit.     

Efficacy of celecoxib,a cyclooxygenase 2–specific inhibitor,in the treatment of ankylosing spondylitis: A six‐week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug

Objective

To evaluate the short‐term efficacy of celecoxib, a cyclooxygenase 2–specific inhibitor, in the treatment of ankylosing spondylitis (AS).

Methods

The study was a 6‐week randomized, double‐blind, placebo‐controlled trial with 3 treatment arms: placebo, ketoprofen 100 mg twice daily, and celecoxib 100 mg twice daily. Patients who had AS according to the modified New York criteria, without peripheral synovitis and with active disease (pain ≥40 mm on a 100‐mm visual analog scale [VAS] and an increase in pain of at least 30% after nonsteroidal antiinflammatory drug withdrawal) were eligible for study. Primary outcome measures were change in pain intensity (VAS) and change in functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI]).

Results

Of the 246 randomized patients, 76 were allocated to receive placebo, 90 ketoprofen, and 80 celecoxib. There were no statistically significant differences between treatment groups at study entry. During the 6 weeks of the study, the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group, with a trend in favor of celecoxib when the 2 active treatments were compared. The mean changes were −13 mm, −21 mm, and −27 mm (P = 0.006) for pain and 1, −6, and −12 (P = 0.0008) for BASFI score in the placebo, ketoprofen, and celecoxib groups, respectively. During treatment, the number of patients reporting epigastric pain was 6 (8%), 13 (14%), and 10 (13%) in the placebo, ketoprofen, and celecoxib groups, respectively.

Conclusion

The results of this study confirm the clinically relevant antiinflammatory effect of celecoxib at a 200‐mg daily dosage, with significant improvement of both pain and function in patients with AS.