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Abstract Objective The aim of this study was to compare radiographic progression in patients with ankylosing spondylitis (AS) treated for up to 2 years with secukinumab (MEASURE 1) with a historical cohort of biologic-naïve patients treated with NSAIDs (ENRADAS). Methods Baseline and 2-year lateral cervical and lumbar spine radiographs were independently evaluated using mSASSS by two readers, who were blinded to the chronology and cohort of the radiographs. The primary endpoint was the proportion of patients with no radiographic progression (mSASSS change ≤ 0 from baseline to year 2). The Primary Analysis Set included patients with baseline (≤ day 30) and post-baseline day 31–743 radiographs. Sensitivity analyses were performed to assess the robustness of the comparison between the two cohorts, as follows: Sensitivity Analysis Set 1 included all patients with baseline (≤ day 30) and year 2 (days 640–819) radiographs; Sensitivity Analysis Set 2 included all patients with baseline and post-baseline (> day 30) radiographs. Results A total of 168 patients (84%) from the MEASURE 1 cohort and 69 (57%) from the ENRADAS cohort qualified for the Primary Analysis Set. Over 2 years, the LS (SE) mean change from baseline in mSASSS for the primary analysis was 0.55 (0.139) for MEASURE 1 vs 0.89 (0.216) for ENRADAS (p = 0.1852). Mean changes from baseline in mSASSS were lower in MEASURE 1 vs ENRADAS for the primary and sensitivity analyses. The proportion of patients with no radiographic progression was consistently higher in the MEASURE 1 vs ENRADAS cohort across all cutoffs for no radiographic progression (change in mSASSS from baseline to year 2 of ≤ 0, ≤ 0.5, ≤ 1, and ≤ 2), but the differences were not statistically significant. Conclusion Secukinumab-treated patients demonstrated a numerical, but statistically non-significant, higher proportion of non-progressors and lower change in mSASSS over 2 years versus a cohort of biologic-naïve patients treated with NSAIDs.

To estimate the incidence of anterior uveitis in patients with ankylosing spondylitis (AS) who underwent anti–tumor necrosis factor (anti‐TNF) therapy, using data from recently performed trials. Data from 4 placebo‐controlled studies with anti‐TNF agents in AS (2 with etanercept and 2 with infliximab) and 3 open‐label studies were analyzed for the prestudy prevalence and the incidence of reported flares of anterior uveitis.A total of 717 patients who received treatment for anterior uveitis during the course of published clinical studies were identified by a systematic literature search using Medline. Followup information on the course of anterior uveitis was available for 397 patients. Of these, 297 were exposed to etanercept and 90 were exposed to infliximab for a total of 430 and 146.4 years, respectively. Among 190 patients who received placebo, the overall exposure was 70.5 years. The frequency of flares of anterior uveitis in the placebo group was 15.6 per 100 patient‐years (95% confidence interval 7.8–27.9), while the patients treated with anti‐TNF agents had a mean of only 6.8 anterior uveitis flares per 100 patient‐years (P = 0.01). Flares of anterior uveitis occurred less frequently (although not significantly) in patients treated with infliximab than in patients treated with etanercept (3.4 per 100 patient‐years and 7.9 per 100 patient‐years, respectively).Treatment of AS patients with biologic agents directed against TNFα is associated with a significant decrease in the number of anterior uveitis flares. This reduction was slightly more marked among patients treated with infliximab, but the difference was not significant. [ABSTRACT FROM AUTHOR]

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. 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). 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. 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. [ABSTRACT FROM AUTHOR]

There is increasing evidence that tumor necrosis factor α (TNFα) is centrally involved in the pathogenesis of ankylosing spondylitis (AS) and other spondylarthritides. This study was designed to investigate the efficacy of anti-TNFα therapy with etanercept, a 75-kd receptor fusion protein, in active AS. This multicenter trial had 2 phases: an initial placebo-controlled period of 6 weeks'' duration and an observational phase lasting 24 weeks. Thirty patients with active AS were included. They were randomized into 2 groups, which received either etanercept (25 mg twice weekly) (n = 14) or placebo (n = 16) for 6 weeks. Then both groups were treated with etanercept. Nonsteroidal antiinflammatory drug (NSAID) treatment could be continued, but disease-modifying antirheumatic drugs (DMARDs) and steroids had to be withdrawn prior to the study. All patients received etanercept for a total of 12 weeks and were followed up for at least 24 weeks. The Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index, Bath AS Metrology Index, pain level on a numeric rating scale, quality of life by the Short Form 36, and C-reactive protein (CRP) level were assessed. The primary outcome parameter was a ≥50% improvement in the BASDAI. Treatment with etanercept resulted in at least a 50% regression of disease activity in 57% of these patients at week 6, versus 6% of the placebo-treated patients (P = 0.004). After the placebo-treated patients switched to etanercept, 56% improved. The mean ± SD BASDAI improved from 6.5 ± 1.2 at baseline to 3.5 ± 1.9 at week 6 in the etanercept group, with no improvement in the placebo group (P = 0.003 between groups). Similarly, pain, function, mobility, and quality of life improved with etanercept but not with placebo at week 6 (P < 0.05). Mean CRP levels decreased significantly with etanercept but not with placebo (P = 0.001). There was ongoing improvement in all parameters in both groups until week 12 and week 18, respectively (i.e., throughout the period of etanercept treatment). Disease relapses occurred a mean ± SD of 6.2 ± 3.0 weeks after cessation of etanercept. No severe adverse events, including major infections, were observed during the trial. This study shows that on a short-term basis (3 months), treatment with etanercept is clearly efficacious in patients with active AS who are receiving NSAID therapy but not DMARDs or steroids. After cessation of therapy, almost all patients experienced a relapse within a few weeks. Thus, it seems probable that etanercept must be administered continuously in most AS patients to achieve permanent inhibition of the inflammatory process. [ABSTRACT FROM AUTHOR]

To localize inflammatory and chronic changes to defined areas in the sacroiliac joints in patients with early-stage compared with late-stage spondylarthritis (SpA), using magnetic resonance imaging (MRI). Using MRI, 93 patients with SpA and inflammatory back pain who had radiographs of the sacroiliac joints were examined, comprising 31 patients with ankylosing spondylitis (AS) and 62 with other SpA subsets, including 48 with undifferentiated SpA (uSpA). MRI was performed using T1-weighted, T2*-weighted, STIR, and dynamic contrast–enhanced (gadolinium diethylenetriaminepentaacetic acid) sequences. Two readers retrospectively analyzed the images by differentiating 9 areas of the sacroiliac joints: the ventral and caudal joint capsule, cavum, subchondral bone, bone marrow, ligament entheses, and ligaments; the sacral and iliac sides were tabulated separately. By MRI, sacroiliitis was more often bilateral in AS (84%) than in uSpA (48%) (P = 0.01). Inflammatory changes were found in a mean ± SD 4.7 ± 2.9 regions/joint, with involvement of 4.5 ± 3.2 regions in early disease versus 5.2 ± 2.3 regions in late disease (P not significant [NS]). Involvement of the iliac side of the sacroiliac joints was found to be more frequent than the sacral side in early disease (58% versus 48%; P < 0.01) as compared with that in late disease (58% versus 63%; P NS). The dorsocaudal parts of the synovial joint and the bone marrow were the most frequently inflamed structures in early disease (P < 0.001 for ventral versus dorsal joint capsule). In contrast, involvement of the entheses was more common in advanced disease (early 43% versus late 86%; P < 0.001). Similarly, the ligaments were more frequently involved in the late stages (early 26% versus late 40%; P = 0.06). Both patterns of bone marrow inflammation (focal and diffuse) were observed in equal frequencies in early and late disease (17% and 42% versus 26% and 43%, respectively; P NS). HLA–B27–positive patients (n = 80) had more entheseal involvement than did HLA–B27–negative patients (n = 13) (60% versus 39%; P = 0.05). HLA–B27–negative patients had a shorter disease duration (2.2 years versus 4.4 years; P = 0.05) and were more often female (62%; P = 0.02). When all pathologic changes were assessed, the STIR sequence (performed in 62 patients) was less sensitive than the contrast-enhanced sequences in that it was not able to show all relevant changes in 27% of these patients (n = 17), failing to reveal inflammation of the cavum in 15 patients and of the bone marrow and joint capsule in 1 patient each. As visualized by MRI, sacroiliitis in SpA is characterized by involvement of different joint structures. Whereas the iliac and the sacral side of the sacroiliac joints are almost equally affected, the dorsocaudal synovial part of the joint is involved significantly more often than the ventral part, especially in early disease. Sacroiliac enthesitis is not a special feature of early sacroiliac inflammation. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Objectives. Anti-tumour necrosis factor therapy with infliximab has been shown to improve signs and symptoms of patients with active ankylosing spondylitis (AS). The objective of this article was to study the effect of infliximab on structural changes in AS over 4 yrs. Methods. Conventional radiographs of the cervical and the lumbar spine of 33 AS patients at baseline (BL), after 2 (FU1) and after 4 yrs (FU2) of infliximab therapy were scored by the modified Stokes ankylosing spondylitis spinal score (mSASSS). Definite baseline damage was defined when at least one syndesmophyte (mSASSS ≥2) was seen. Definite radiographic progression was defined as a change from 0 or 1 to syndesmophytes or ankylosis (mSASSS ≥2). Results. The mean change over 4 yrs was 1.6 ± 2.6 mSASSS units (P = 0.001), (0.9 ± 2.3 for BL–FU1 vs 0.7 ± 1.6 for FU1–FU2). This is less radiographic progression in comparison with published data from the OASIS cohort (4.4 within 4 yrs). Definite radiographic progression was found in 10/33 (30.3%) patients for BL–FU2. Patients with definite damage at BL developed more chronic changes at FU2 (2.3 ± 3.1, P = 0.003) than those with no damage at BL (0.7 ± 1.5, P = 0.08). Four out of seven patients with no damage at BL showed radiographic deterioration after 4 yrs. The change of the mean mSASSS in comparison with BL was significantly different after 2 (P = 0.007) but not after 4 yrs of infliximab therapy. Conclusions. There is some radiographic progression after 2 and 4 yrs of infliximab therapy in AS patients. A comparison with the historical OASIS cohort suggests that infliximab may decelerate progression of structural changes. Larger studies are needed to confirm this finding. [ABSTRACT FROM AUTHOR]