Assessment Of Radiographic Progression Research Articles

Sustained Remission in Rheumatoid Arthritis: Time to Withdraw Treatment?

With increasing numbers of patients with rheumatoid arthritis achieving sustained remission, medication withdrawal is an important consideration to reduce polypharmacy and associated adverse events. An article from the journal Arthritis & Rheumatology (1) explores the treatment withdrawal options for patients on etanercept and methotrexate combination therapies and suggests methotrexate withdrawal has the least impact on disease worsening. There are limitations in the study, including the use of only one disease activity score and no assessment of radiographic progression, but, overall, the article provides a good framework for future studies on treatment withdrawal options and the possibility of medication reduction for patients.

Assessment of radiographic progression in patients with rheumatoid arthritis treated with tofacitinib in long-term studies.

ObjectivesTofacitinib is an oral Janus kinase inhibitor for the treatment of RA. We evaluated radiographic progression in tofacitinib-treated patients with RA for up to 3 years in two pooled long-term extension (LTE) studies (ORAL Sequel; A3921041) (primary analysis), and for up to 5 years using data integrated from one phase (P)2 (A3921068), two P3 (ORAL Start; ORAL Scan) and two LTE studies (exploratory analysis).MethodsIn LTE studies, patients received tofacitinib 5 mg twice daily (BID) or 10 mg BID as monotherapy or with conventional synthetic (cs)DMARDs. Radiographic outcomes up to 3 years: least squares mean (LSM) change from baseline in van der Heijde modified Total Sharp Score (ΔmTSS), erosion score (ΔES) and joint space narrowing (ΔJSN) score; proportion of patients with no radiographic progression (ΔmTSS ≤0.5); proportion of patients with no new erosions (ΔES ≤0.5). ΔmTSS was evaluated for up to 5 years in an exploratory analysis.ResultsFor all tofacitinib-treated patients with radiographic data available at LTE month 36 (n = 414), LSM ΔmTSS was 1.14, LSM ΔES was 0.66, LSM ΔJSN was 0.74, and 74.3% and 86.2% of patients showed no radiographic progression and no new erosions, respectively. Similar values were observed regardless of tofacitinib dose, or whether patients received tofacitinib as monotherapy or with csDMARDs. In an exploratory analysis of integrated P2/P3/LTE studies, LSM ΔmTSS was 3.34 at month 60 (n = 269).ConclusionLimited progression of structural damage was observed in tofacitinib-treated patients up to 5 years, with similar results for tofacitinib used as monotherapy or combination therapy up to 3 years.Trial registrationClinicalTrials.gov (http://clinicaltrials.gov): NCT01164579; NCT01039688; NCT00847613; NCT00413699; NCT00661661.

PP11. Assessment of radiographic progression in patients with systemic juvenile idiopathic arthritis treated with tocilizumab: 2-year data from tender

PP11. Assessment of radiographic progression in patients with systemic juvenile idiopathic arthritis treated with tocilizumab: 2-year data from tender

289. Assessment of Radiographic Progression in Patients with Systemic Juvenile Idiopathic Arthritis Treated with Tocilizumab: 2-Year Results from the Tender Trial

289. Assessment of Radiographic Progression in Patients with Systemic Juvenile Idiopathic Arthritis Treated with Tocilizumab: 2-Year Results from the Tender Trial

A11: Assessment of Radiographic Progression in Patients With Polyarticular‐Course Juvenile Idiopathic Arthritis Treated With Tocilizumab: 2‐Year Data From CHERISH

Background/Purpose:The phase 3 CHERISH trial demonstrated the efficacy of tocilizumab (TCZ), an interleukin‐6 receptor inhibitor, in patients with polyarticular‐course juvenile idiopathic arthritis (pcJIA). This analysis investigated the progression of radiographic joint damage in patients with pcJIA treated with TCZ for up to 104 weeks in CHERISH.Methods:Patients 2 to 17 years old with ≥6 months' active pcJIA for whom methotrexate failed received open‐label (OL) TCZ according to body weight (BW) (BW ≥30 kg, 8 mg/kg [n = 119]; BW <30 kg, randomly assigned 1:1 to 8 mg/kg [n = 34] or 10 mg/kg [n = 35]) every 4 weeks for 16 weeks. At 16 weeks, eligible patients (≥JIA ACR30 response) entered a 24‐week, randomized, double‐blind withdrawal period and were assigned 1:1 to placebo or continued TCZ. All patients entered an OL extension through week 104. Those receiving TCZ in all 3 parts were included in the continuous TCZ subgroup for which key radiographic end points were assessed. Radiographic progression was indicated as a positive change in adapted Sharp/van der Heijde score () (aSH) and/or a negative change in Poznanski score (), assessed on hand and wrist radiographs, from baseline to weeks 52 and 104.Results:Baseline and ≥1 postbaseline aSH and Poznanski scores were available for 45 and 35 patients, respectively, in the continuous TCZ subgroup and for 87 and 61 patients, respectively, in the total population. Reasons for missing data included early withdrawal, no consent, or unreadable radiographs (because of advanced damage resulting in unreliable measurements or growth plate fusion in postpubertal children), preventing assessment of Poznanski scores. Baseline demographics and disease characteristics were balanced for aSH and Poznanski populations and were similar to those for the full study population. At weeks 52 and 104, median changes from baseline aSH score of 0.5 (p = 0.70) and −1.0 (p = 0.11), respectively, and median changes from baseline Poznanski score of 0.3 (p = 0.07) and 0.6 (p = 0.004), respectively, indicating a lack of radiographic progression. With a cutoff of the smallest detectable difference, no radiographic progression was seen in 87.5% and 97.1% of patients based on aSH scoring and 93.5% and 96.0% of patients based on Poznanski scoring at weeks 52 and 104, respectively. Comparable proportions of the total radiographic population, including those exposed to placebo, remained radiographic progression free at week 104. Among the radiographic population, the annualized rates of progression to week 104 for aSH and Poznanski scores were 0.00 and 0.18, respectively.Conclusion:TCZ halted the progression of radiographic damage, leaving a large majority of pcJIA patients free of radiographic progression after 2 years of treatment.

A66: Assessment of Radiographic Progression in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Tocilizumab: 2‐Year Results From the TENDER Trial

Background/Purpose: A phase 3 trial (TENDER) demonstrated the efficacy of the interleukin-6 receptor inhibitor tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (sJIA) ([1, 2]). The aim of this study was to investigate the progression of radiographic joint damage in patients with sJIA treated with TCZ for up to 2 years in TENDER. Methods: One hundred twelve patients 2 to 17 years old with active, refractory sJIA of ≥6 months' duration and inadequate response to previous nonsteroidal anti-inflammatory drugs and oral corticosteroids were enrolled in TENDER. Patients were randomly assigned 2:1 to receive TCZ according to body weight (12 mg/kg <30 kg or 8 mg/kg ≥30 kg) or placebo intravenously every 2 weeks for 12 weeks. Patients then received open-label TCZ in the ongoing long-term extension. Radiographic progression was calculated as change in adapted Sharp/van der Heijde score (aSH) score and/or Poznanski score, assessed on hand and wrist radiographs, from baseline to weeks 52 and 104. Radiographic progression was indicated by a positive aSH score change or a negative Poznanski score change. Clinical efficacy end points included American College of Rheumatology (ACR) Pediatric (Pedi) 70/90 responses. Results: Baseline and ≥1 postbaseline aSH and Poznanski scores were available for 47 and 33 patients, respectively (reasons for missing x-rays: early withdrawal, no consent, unreadable x-rays). Baseline characteristics for patients with radiographic data were similar in the whole TCZ population (1). Patients with assessable aSH/Poznanski scores had 5.2-/4.8-year disease duration, 21.3/19.2 active joints, 20.0/18.2 joints with limitation of movement, and 53.9/59.2 mm/h erythrocyte sedimentation rate. At weeks 52 and 104, 20 and 19 patients, respectively, had aSH progression, and 8 and 8 patients, respectively, had Poznanski score progression. Median changes in aSH score from baseline to weeks 52 and 104 were 0 and 0.5, respectively (1). Median changes in Poznanski score from baseline to weeks 52 and 104 were 0.29 and 0.16, respectively (1). Table 1. Week 52 Week 104 a IQR, interquartile range. aSH score (n = 47), median (IQR) 0.00 (−8.70: 4.00) 0.50 (−7.50: 12.00) Poznanski score (n = 33), median (IQR) 0.29 (−0.05: 1.05) 0.16 (−0.01: 1.04) ACR Pedi 70 (n = 112), n/N (%) 92/106 (86.8) 57/65 (87.7) ACR Pedi 90 (n = 112), n/N (%) 67/106 (63.2) 46/65 (70.8) Conclusion: Although changes in radiographic scores over time were seen in many patients, on average, patients with sJIA did not experience noticeable progression of radiographic damage over 2 years of treatment with TCZ.

PReS-FINAL-2134: Assessment of radiographic progression in patients (pts) with systemic juvenile idiopathic arthritis (sjia) treated with tocilizumab (TCZ): 2-year results from the tender trial

A phase 3 trial (TENDER) demonstrated the efficacy of the interleukin-6 receptor inhibitor TCZ in pts with sjia [1,2].

Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis: results of the RAPID-PsA 24-week phase III double-blind randomised placebo-controlled study of certolizumab pegol

ObjectivesTo report the effect of different imputation methodologies on the assessment of radiographic progression in clinical trials.MethodsThe 216-week RAPID-psoriatic arthritis (PsA) (NCT01087788) trial of certolizumab pegol (CZP) in patients with...

An Analysis of the Use of the Kellgren and Lawrence Grading System to Evaluate Peritalar Arthritis Following Total Ankle Arthroplasty

The Kellgren and Lawrence grading system (KLGS) has been used throughout the literature for the radiographic staging of osteoarthritis (OA) of the peritalar joints. Despite its widespread use, the KLGS has never been validated for use in this clinical circumstance. The purpose of this study was to determine the inter- and intrarater reliability of the KLGS in the assessment of radiographic progression of OA in the peritalar joints following total ankle replacement (TAR). One hundred twenty pre- and minimum 5-year postoperative weight-bearing lateral radiographs following 60 consecutive cases of TAR were utilized. Each individual film was considered separately for the purposes of this study. Of those films, 93 and 98 were found to have adequate visualization of the subtalar (STJ) and talonavicular (TNJ) joints, respectively. Three qualified reviewers graded the films according to the KLGS on 2 separate occasions, with 1 month separating the 2 readings. The results were analyzed for intra- and interobserver reliability. The degree of agreement was analyzed using the weighted kappa (κ(w)) statistic, Fleiss's kappa (Fleiss's κ), and percentage agreement Interrater agreements were moderate (κ(w) = 0.37 ± 0.06; Fleiss's κ = 0.21 ± 0.03) for the STJ to fair (κ(w) = 0.43 ± 0.06; Fleiss's κ = 0.25 ± 0.03) for the TNJ. Intrarater agreements for the STJ were moderate (mean κ(w) = 0.43 ± 0.07) and moderate for the TNJ as well (mean κ(w) = 0.46 ± 0.07). The reliability of the KLGS, although not originally designed for use in the setting of inflammatory arthropathy, was not notably affected when being used to grade inflammatory versus noninflammatory arthropathy. The KLGS is likely not a reliable tool for grading the degree of OA present in the peritalar joints prior to treatment and following TAR for research purposes. Using the KLGS in the setting of inflammatory arthritis versus OA did not produce any notable differences in the observed reliability. It is important to remember this has not been assessed in the clinical environment. Further work is required to determine the optimal method for assessment of peritalar OA. Level II, prospective comparative study.

Measurement error in the assessment of radiographic progression in rheumatoid arthritis (RA) clinical trials: the smallest detectable change (SDC) revisited

ObjectivesTo evaluate if the mean smallest detectable change (SDC) of multiple time intervals using the Bland & Altman (B&A) levels of agreement (LoA) method is an appropriate surrogate for the...

Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years

IntroductionAnkylosing spondylitis (AS) is a chronic rheumatic disease associated with spinal inflammation that subsequently leads to progression of structural damage and loss of function. The fully human anti-tumor necrosis factor (anti-TNF) antibody adalimumab reduces the signs and symptoms and improves overall quality of life in patients with active AS; these benefits have been maintained through 2 years of treatment. Our objective was to compare the progression of structural damage in the spine in patients with AS treated with adalimumab for up to 2 years versus patients who had not received TNF antagonist therapy.MethodsRadiographs from patients with AS who received adalimumab 40 mg every other week subcutaneously were pooled from the Adalimumab Trial Evaluating Long-Term Efficacy and Safety for Ankylosing Spondylitis (ATLAS) study and a Canadian AS study (M03-606). Radiographic progression from baseline to 2 years in the spine of adalimumab-treated patients from these two studies (adalimumab cohort, n = 307) was compared with an historic anti-TNF-naïve cohort (Outcome in AS International Study [OASIS], n = 169) using the modified Stoke AS Spine Score (mSASSS) method.ResultsmSASSS results were not significantly different between the adalimumab cohort and the OASIS cohort, based on baseline and 2-year radiographs. Mean changes in mSASSS from baseline to 2 years were 0.9 for the OASIS cohort and 0.8 for the adalimumab cohort (P = 0.771), indicating similar radiographic progression in both groups. When results for patients in the OASIS cohort who met the baseline disease activity criteria for the ATLAS and Canadian studies (OASIS-Eligible cohort) were analyzed, there was no significant difference in mean change in mSASSS from baseline to 2 years between OASIS-Eligible patients and adalimumab-treated patients; the mean changes in mSASSS were 0.9 for the OASIS-Eligible cohort and 0.8 for the adalimumab cohort (P = 0.744).ConclusionsTwo years of treatment with adalimumab did not slow radiographic progression in patients with AS, as assessed by the mSASSS scoring system, when compared with radiographic data from patients naïve to TNF antagonist therapy.Trial registrationCanadian study (M03-606) ClinicalTrials.gov identifier: NCT00195819; ATLAS study (M03-607) ClinicalTrials.gov identifier: NCT00085644.

Radiography of rheumatoid arthritis in the time of increasing drug effectiveness.

Recent clinical development programs for new therapeutic agents in rheumatoid arthritis have included assessment of radiographic progression comparing changes with treatment to placebo and active controls. Studies now use reliable methods of assessment and sufficient study length to detect radiographic changes. Although patient populations and characteristics differ, and radiographic scoring methods vary, the direction of a series of studies appears to indicate that leflunomide (LEF), methotrexate (MTX), sulfasalazine (SSZ), etanercept, infliximab, and IL-1ra are all effective in retarding radiographic progression, as measured by erosions and joint space narrowing. Interpretation of radiograph data in future trials will be aided by utilization of common reading methods and by continuing comparison across differing rheumatoid arthritis protocol populations.