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.

     

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.

     

Different response to rituximab in tumor necrosis factor blocker–naive patients with active ankylosing spondylitis and in patients in whom tumor necrosis factor blockers have failed: A twenty‐four–week clinical trial

Objective

Histologic studies have shown B cell clusters in the subchondral bone marrow of the spine of patients with ankylosing spondylitis (AS). An immunotherapy targeting B cells in AS is therefore of interest. We undertook this study to examine the efficacy and safety of rituximab in patients with AS refractory to nonsteroidal antiinflammatory drugs in whom previous treatment with tumor necrosis factor α (TNFα) blockers either had not been tried or had failed.

Methods

In this phase II clinical trial, 1,000 mg rituximab was administered intravenously at baseline and at week 2 in 20 patients with active AS. Ten of these patients had never received TNF blockers, and treatment with TNF blockers had failed in the other 10 patients. The primary end point was a 20% improvement in disease activity at week 24 according to the criteria of the Assessment of SpondyloArthritis international Society (an ASAS20 response).

Results

Seventy‐five percent of the patients were male, 90% were HLA–B27 positive, their mean age was 39.7 years, and their mean disease duration was 16.8 years. Patients had active disease, defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4. While there was no clear response at week 24 in the group in whom TNF blockers had failed (30% had achieved an ASAS20 response, 10% had achieved an ASAS40 response, none had achieved partial remission according to the ASAS criteria, and none had achieved 50% improvement on the BASDAI [a BASDAI50 response] beyond an expected placebo response), we observed a good improvement in the TNF blocker–naive group at week 24 (50% had achieved an ASAS20 response, 40% had achieved an ASAS40 response, 30% had achieved partial remission according to the ASAS criteria, and 50% had achieved a BASDAI50 response).

Conclusion

Although rituximab does not seem to be effective in patients with AS that does not respond to TNF blockers, it had significant efficacy in TNF blocker–naive patients. Therefore, further controlled trials with B cell–directed therapies should be performed in TNF blocker–naive AS patients in the future.

     

Serum levels of matrix metalloproteinase 3 and macrophage colony‐stimulating factor 1 correlate with disease activity in ankylosing spondylitis

Objective

To assess the usefulness of measuring serum matrix metalloproteinase 3 (MMP‐3) and macrophage colony‐stimulating factor (M‐CSF) in patients with ankylosing spondylitis (AS).

Methods

Serum levels of MMP‐3 and M‐CSF were measured in AS patients who did and did not receive infliximab treatment. These were compared with those of 28 healthy subjects.

Results

In the group of AS patients not treated with biologics, both M‐CSF and MMP‐3 correlated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) values, but not with each other. Logistic regression analysis showed that MMP‐3 values were high in those with severely active disease. Infusions of infliximab in AS patients led to a significant decrease in the values of the BASDAI as well as the serum MMP‐3, but no change in the serum M‐CSF values.

Conclusion

MMP‐3 and M‐CSF are potentially useful markers of AS disease activity.

     

Fatigue in patients with ankylosing spondylitis: A comparison with the general population and associations with clinical and self‐reported measures

Objective

To investigate 1) levels of fatigue in patients with ankylosing spondylitis (AS) compared with the general population; 2) the relationships between fatigue and demographic, self‐reported, and clinical measures; and 3) the performance of both a generic and a disease‐specific measure of fatigue.

Methods

Patients with AS (n = 152) were compared with people from the general population (n = 2,323). Fatigue was assessed by the Short Form 36 (SF‐36) vitality scale and the fatigue item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Other measures of self‐reported health included BASDAI for disease activity, Bath Ankylosing Spondylitis Functional Index for functional abilities, and the SF‐36 for mental health. Clinical measures comprised Bath Ankylosing Spondylitis Metrology Index for joint mobility and erythrocyte sedimentation rate and C‐reactive protein as inflammatory markers. The explanatory power of demographic, self‐reported, and clinical measures was examined in a block regression model.

Results

The mean ± SD SF‐36 vitality score was 43 ± 24 in the patients and 60 ± 21 in the general population (P < 0.001). The SF‐36 vitality and the BASDAI fatigue scores were consistently associated with measures of mental health and disease activity. Clinical measures did not show explanatory power. A cutoff at 70 mm on the BASDAI fatigue item implied specificity of 0.77 and sensitivity of 0.82.

Conclusion

Self‐reported measures of disease activity and mental health contributed significantly to explain fatigue, whereas clinical measures of inflammation and joint mobility did not. The BASDAI fatigue item reached acceptable sensitivity and specificity with a cutoff at 70 mm when using the low vitality scores of SF‐36 as an external indicator.

     

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.

     

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.

     

Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: A multicenter,randomized, double‐blind,placebo‐controlled study

Objective

To compare the efficacy of adalimumab versus placebo in reducing spinal and sacroiliac (SI) joint inflammation, by magnetic resonance imaging (MRI) in patients with active ankylosing spondylitis (AS).

Methods

This was a randomized, multicenter, double‐blind, placebo‐controlled study. Patients (n = 82) received 40 mg adalimumab or placebo every other week during an initial 24‐week double‐blind period. MRIs of both the spine and SI joints were obtained at baseline, week 12, and week 52. Spinal and SI joint inflammation were measured using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index.

Results

The spine SPARCC score in placebo‐treated patients increased by a mean of 9.4% from baseline, compared with a mean decrease of 53.6% in adalimumab‐treated patients (P < 0.001); the SI joint SPARCC score decreased by a mean of 12.7% from baseline in placebo‐treated patients and by 52.9% in adalimumab‐treated patients (P = 0.017). The response in adalimumab‐treated patients was maintained at week 52. Placebo‐treated patients were switched to open‐label adalimumab treatment at week 24 and experienced similar reductions in spinal and SI joint inflammation by week 52. Similar large reductions in the spine and SI joint SPARCC scores were noted, even in patients who failed to meet the ASsessment in Ankylosing Spondylitis (International Working Group) criteria (nonresponders) at 12 weeks. In adalimumab‐treated patients, a reduced C‐reactive protein concentration at week 12 was significantly associated with improvement in the spine SPARCC score (P = 0.018).

Conclusion

Adalimumab significantly reduced both spinal and SI joint inflammation in patients with active AS after 12 weeks of treatment, and these improvements were maintained for up to 52 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.

     

Use of a numerical rating scale as an answer modality in ankylosing spondylitis–specific questionnaires

Objectives

To determine the agreement of scores on the original visual analog scale (VAS) or Likert scale of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Dougados Functional Index (DFI) with scores on a numerical rating scale (NRS). To assess the reproducibility and responsiveness of the instruments with the original scale and NRS.

Methods

Five hundred thirty‐six patients with ankylosing spondylitis from the Netherlands, Mexico, and Switzerland completed a questionnaire in which all questions from the BASDAI, BASFI, and DFI were presented twice in random order with an 11‐point NRS and either a 10‐cm VAS (BASDAI and BASFI) or a 5‐point Likert scale (DFI). Agreement of scores using Bland‐Altman plots and intraclass correlation coefficients (ICCs), reproducibility using ICCs, and responsiveness were assessed.

Results

Large variability between the scores on the original scales and the NRS was found in individual questions of all 3 questionnaires, although total scores showed ICCs of at least 0.88. Reproducibility of all answer modalities showed low ICCs in individual questions, but moderate to good ICCs in total scores (Dutch group 0.62–0.89; Mexican group 0.53–0.72). Moderate to large effects (0.48–1.04) were found in responsiveness scores in the 3 questionnaires. No major differences in reproducibility and responsiveness between the answer modalities were found.

Conclusion

Although large variability between the scores on the original answer scales and the NRS was observed, the BASDAI, BASFI, and DFI can be administered with an NRS, which does not show important differences compared with the original scales.

     

Improvement in hemoglobin levels in patients with ankylosing spondylitis treated with infliximab

Objective

Anemia is a common complication in patients with inflammatory diseases such as ankylosing spondylitis (AS). This post hoc analysis of a large, randomized, placebo‐controlled trial examined the effect of infliximab on hemoglobin levels, physical function, and fatigue in patients with AS.

Methods

Patients received infliximab 5 mg/kg (n = 188) or placebo (n = 68) at weeks 0, 2, 6, 12, and 18. Hemoglobin, interleukin‐6 (IL‐6), and C‐reactive protein (CRP) levels, fatigue (visual analog scale [VAS]), physical function (Bath Ankylosing Spondylitis Functional Index [BASFI]), and disease activity were evaluated at baseline and week 24. Anemia was defined as a hemoglobin level <12 gm/dl for women and <13 gm/dl for men.

Results

At baseline, 11 placebo group patients (16.2%) and 37 infliximab group patients (19.7%) had anemia. Of these, more infliximab‐treated patients achieved normal hemoglobin levels at week 24 compared with patients receiving placebo (70.3% versus 27.3%; P = 0.0155). Infliximab‐treated patients had significant improvements in mean hemoglobin concentration (0.7 gm/dl versus ?0.3 gm/dl), BASFI score (?2.1 versus ?0.2), and fatigue VAS score (?2.4 versus ?0.4) compared with placebo patients (P < 0.001). Multiple regression analyses showed that improvements in hemoglobin level were significantly and independently associated with improvements in physical function and fatigue. Infliximab‐treated patients with elevated CRP or IL‐6 levels at baseline were more likely than those with low levels to have improvement in hemoglobin levels.

Conclusion

Infliximab treatment significantly decreased the proportion of AS patients with anemia and improved hemoglobin levels compared with placebo. Improvement in hemoglobin level was independently associated with improvements in physical function and fatigue.

     

Mental health status and leisure‐time physical activity contribute to fatigue intensity in patients with spondylarthropathy

Objective

To examine the relationship between disease‐related variables, leisure‐time physical activity (LTPA), and mental health status with fatigue severity in patients with spondylarthropathy (SpA).

Methods

Sixty‐six SpA patients completed questionnaires assessing disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), functional ability (Bath Ankylosing Spondylitis Functional Index), and health‐related quality of life (Short Form 36). LTPA patterns, demographics, and disease‐related data were obtained by interview. A clinical examination determined tender point count. Fatigue was assessed with the BASDAI fatigue item.

Results

The mean BASDAI fatigue score was 5.5 (SD = 2.7) with 59% of the sample obtaining a score ≥5. Disease activity, functional disability, and worse mental health contributed to greater fatigue (R² = 0.56). The relationship between exercise duration and fatigue intensity was moderated by mental health status. For patients with poorer mental health scores, exercise did not influence fatigue severity. However, for patients reporting better mental health status, engaging in more LTPA decreased fatigue severity.

Conclusion

In addition to increased disease activity and functional disability, greater fatigue severity in SpA is associated with poorer mental health status. Integrating regular leisure physical activity into the comprehensive treatment of SpA may be useful for modulating fatigue.

     

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.

     

Is disease severity in ankylosing spondylitis genetically determined?

Objective

To assess the role of genes and the environment in determining the severity of ankylosing spondylitis.

Methods

One hundred seventy‐three families with >1 case of ankylosing spondylitis were recruited (120 affected sibling pairs, 26 affected parent–child pairs, 20 families with both first‐ and second‐degree relatives affected, and 7 families with only second‐degree relatives affected), comprising a total of 384 affected individuals. Disease severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional impairment was determined using the Bath Ankylosing Spondylitis Functional Index (BASFI). Disease duration and age at onset were also studied. Variance‐components modeling was used to determine the genetic and environmental components contributing to familiality of the traits examined, and complex segregation analysis was performed to assess different disease models.

Results

Both the disease activity and functional capacity as assessed by the BASDAI and the BASFI, respectively, were found to be highly familial (BASDAI familiality 0.51 [P = 10⁻⁴], BASFI familiality 0.68 [P = 3 × 10⁻⁷]). No significant shared environmental component was demonstrated to be associated with either the BASDAI or the BASFI. Including age at disease onset and duration of disease as covariates made no difference in the heritability assessments. A strong correlation was noted between the BASDAI and the BASFI (genetic correlation 0.9), suggesting the presence of shared determinants of these 2 measures. However, there was significant residual heritability for each measure independent of the other (BASFI residual heritability 0.48, BASDAI 0.36), perhaps indicating that not all genes influencing disease activity influence chronicity. No significant heritability of age at disease onset was found (heritability 0.18; P = 0.2). Segregation studies suggested the presence of a single major gene influencing the BASDAI and the BASFI.

Conclusion

This study demonstrates a major genetic contribution to disease severity in ankylosing spondylitis. As with susceptibility to ankylosing spondylitis, shared environmental factors play little role in determining the disease severity.

     

Physical function and health‐related quality of life of Spanish patients with ankylosing spondylitis

Objective

To determine the physical function and the quality of life (QOL) of Spanish patients with ankylosing spondylitis (AS), and to study the reliability of the Spanish version of the Bath Ankylosing Spondylitis Functional Index (BASFI).

Methods

Clinimetric variables, including Spanish BASFI (test‐retest), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), QOL instruments (Short Form 36 [SF‐36] and European Quality of Life Questionnaire [EuroQol]), Bath Ankylosing Spondylitis Metrology Index (BASMI), and chest expansion, were assessed.

Results

A total of 92 patients were included: 69 males (75%), age (mean ± SD) 40.7 ± 9.1 years, and disease duration 11 ± 7.8 years. The scores (mean ± SD) were (from 0 the best to 10 the worst): BASFI 4.3 ± 2.4; BASDAI 4.5 ± 2.2; global SF‐36 5.5 ± 2.1; SF‐36 physical function 3.8 ± 2.5; SF‐36 physical scale 4.9 ± 2.7; SF‐36 mental scale 3.7 ± 2.7; SF‐36 physical role limitations 5.6 ± 4.4; SF‐36 general health 5.5 ± 2.1; SF‐36 pain 5.4 ±2.8; SF‐36 vitality 5.1 ± 2; EuroQoL rating scale 3.9±2.1; EuroQol health profile (from 0 the best to 2 the worst) 0.6 ± 0.4; and BASMI 4.7 ± 1.6. Significant association was found between BASFI and SF‐36 physical function domain (r = 0.75, R² = 0.56, P < 0.0001). BASFI Cronbach's alpha was 0.92, Spearman's rho = 0.91, P < 0.0001.

Conclusions

Physical function and QOL are deteriorated in AS. The physical domain is more impaired than the mental one. The SF‐36 and the health profile of the EuroQol may be used as generic instruments to measure health‐related QOL. Spanish BASFI index is a reliable instrument.

     

Responsiveness and discriminative capacity of the assessments in ankylosing spondylitis disease‐controlling antirheumatic therapy core set and other outcome measures in a trial of etanercept in ankylosing spondylitis

Objective

To investigate the responsiveness and discriminative capacity, and the relationship between both, of instruments selected for the disease‐controlling antirheumatic therapy (DC‐ART) core set by the Assessments in Ankylosing Spondylitis Working Group (ASAS).

Methods

Responsiveness and discriminative capacity of different measures reflecting disease activity and function, either included in the ASAS DC‐ART core set or not, were evaluated in a randomized controlled clinical trial comparing etanercept with placebo in patients with ankylosing spondylitis. Guyatt's method was used as the primary analysis for responsiveness, and Student's t‐test for discriminative capacity.

Results

At day 28 of therapy, almost all measures indicated moderate to large responsiveness in the etanercept group (Guyatt 0.60–3.11). Some scales of the Short Form 36 (general health, mental component summary, and role emotional), the modified Schober's test, and the Fatigue Severity Scale were not responsive. The results were similar if analyzed at day 112 of therapy. Peripheral joint counts, joint scores, and occiput‐to‐wall distance could not be evaluated due to a floor effect. In general, the relation between responsiveness and discriminative capacity was strong: Measures that demonstrated high responsiveness also showed high between‐group t values.

Conclusion

Measures included in the ASAS DC‐ART core set, except modified Schober's test, have good responsiveness and good discriminatory capacity. Some measures could not be evaluated due to a floor effect.

     

Could the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) be a valid measure of disease activity in patients with psoriatic arthritis?

Objective

To determine whether the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) could be a valid indicator of disease activity in psoriatic arthritis (PsA).

Methods

Patients with PsA identified from a disease‐register and case‐note review answered a questionnaire by mail (n = 133); some patients (n = 86) consented to examination. In a second sample of 47 consecutive clinic attendees with PsA, logistic regression examined the independent contribution of BASDAI to disease activity, as judged by treatment decisions at that time.

Results

BASDAI correlated highly with patient perception of disease activity (r = 0.739) and there was no significant effect of the pattern of disease (axial or peripheral) on this relationship. However, only physician perception of disease activity was significantly associated with high or low disease activity (odds ratio 18.4, 95% confidence interval 2.9–118.3). BASDAI, patient perception, and erythrocyte sedimentation rate failed to contribute significantly to the model.

Conclusion

BASDAI performs similarly for axial and peripheral PsA but does not correlate well with external indicators of disease activity, such as treatment decisions.

     

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.

     

Golimumab,a new human tumor necrosis factor α antibody,administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty‐four–week efficacy and safety results of a randomized,placebo‐controlled study

Objective

To assess the efficacy and safety of golimumab in patients with active psoriatic arthritis (PsA).

Methods

Adult patients with PsA who had at least 3 swollen and 3 tender joints and active psoriasis were randomly assigned to receive subcutaneous injections of placebo (n = 113), golimumab 50 mg (n = 146), or golimumab 100 mg (n = 146) every 4 weeks through week 20. Efficacy assessments through week 24 included the American College of Rheumatology 20% improvement criteria (ACR20), the Psoriasis Area and Severity Index (PASI) in patients in whom at least 3% of the body surface area was affected by psoriasis at baseline, the Short Form 36 Health Survey (SF‐36), the disability index of the Health Assessment Questionnaire (HAQ), the Nail Psoriasis Severity Index (NAPSI), the physician's global assessment of psoriatic nail disease, and enthesitis (using the PsA‐modified Maastricht Ankylosing Spondylitis Enthesitis Score [MASES] index).

Results

At week 14, 48% of all patients receiving golimumab, 51% of patients receiving golimumab 50 mg, and 45% of patients receiving golimumab 100 mg achieved an ACR20 response (the primary end point), compared with 9% of patients receiving placebo (P < 0.001 for all comparisons). Among the 74% of patients in whom at least 3% of the body surface area was affected by psoriasis at baseline, 40% of those in the golimumab 50 mg group and 58% of those in the golimumab 100 mg group had at least 75% improvement in the PASI at week 14 (major secondary end point), compared with 3% of placebo‐treated patients (P < 0.001 for both doses). Significant improvement was observed for other major secondary end points (the HAQ and the SF‐36), the NAPSI, the physician's global assessment of psoriatric nail disease, and the PsA‐modified MASES index in each golimumab group compared with placebo. This efficacy was maintained through week 24. Golimumab was generally well tolerated.

Conclusion

Treatment with golimumab at doses of 50 mg and 100 mg significantly improved active PsA and associated skin and nail psoriasis through week 24.

     

Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis,before and after successful therapy with infliximab: Evaluation of a new scoring system

Objective

To evaluate a magnetic resonance imaging (MRI) scoring system for the assessment of spinal inflammation in patients with ankylosing spondylitis (AS) who participated in a randomized, placebo‐controlled trial of infliximab, and to examine whether infliximab is also effective for the reduction of MRI‐proven spinal inflammation.

Methods

Twenty patients with AS (9 women and 11 men, mean age 40.9 years) were examined at baseline and after 3 months. Nine patients had received infusions of infliximab (5 mg/kg body weight) at weeks 0, 2, and 6, and 11 patients had received placebo. Three MRI sequences and 2 scoring systems were used. Chronic lesions were evaluated by T1‐weighted turbo spin‐echo (TSE) sequences and were assigned a chronicity score. Active lesions were evaluated either by repetition of T1‐weighted TSE sequences after infusion of gadolinium–diethylenetriaminepentaacetic acid (Gd‐DTPA) or by short tau inversion recovery (STIR) sequences, and were assigned an activity score. The 40 images were evaluated twice by 2 readers who were blinded to the names of the patients and the dates of the examinations, and were analyzed in relation to the clinical results.

Results

Active spinal lesions were detected in 15 of 20 patients (75%); the frequency as determined by STIR was equal in the 2 groups. At baseline, the total MRI scores determined using Gd‐DTPA, STIR, and T1 were 112.5, 156, and 253.5, respectively. The interrater variance and intrarater variance were, respectively, 6.4 and 7.7 for the active lesion score as determined by Gd‐DTPA, 15.7 and 5.3 for the active lesion score as determined by STIR sequence, and 167.3 and 75.5 for the chronic lesion score as determined by T1 sequence. Based on the means of the scores assigned by the 2 readers, the active lesion score as determined by Gd‐DTPA improved by 40% in the infliximab group compared with 6% in the placebo group, the active lesion score as determined by STIR improved by 60% in the infliximab group but deteriorated by 21% in the placebo group, and the chronic lesion score as determined by T1 improved by 7% in the infliximab group but worsened by 35% in the placebo group. Five patients in the infliximab group and 2 in the placebo group were clinical responders. The acute MRI changes correlated with clinical improvement as assessed by the Bath Ankylosing Spondylitis Disease Activity Index.

Conclusion

This novel MRI scoring system performed well in assessing acute inflammation by using STIR and post–Gd‐DTPA sequences. In correlation with clinical improvement in patients with active AS who were treated with infliximab, significant regression of spinal inflammation was shown by using the MRI activity scores.