ACHILLES is a 2-treatment arm, randomized, parallel-group, double-blind, placebo-controlled study in patients with PsA or axSpA . Patients were randomized to receive subcutaneous (s.c.) secukinumab 150 mg, 300 mg or placebo at baseline, weeks 1, 2, 3, and 4, followed by once every 4 weeks. At week 24, patients on placebo were switched to secukinumab 150 or 300 mg.
Patients (≥18 years) with active SpA and clinical heel enthesitis confirmed by imaging were eligible to participate in the trial. Active SpA was defined as either axSpA with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 (0-10) at baseline or PsA fulfilling the CASPAR (ClASsification for Psoriatic ARthritis) criteria with symptoms for at least 6 months and ≥1 tender joint out of 78 and ≥1 swollen joint out of 76 at baseline. Clinical heel enthesitis was defined as swelling and tenderness at the insertional site of the Achilles tendon into the calcaneus (binary pain assessment). Heel enthesitis must have been refractory to standard treatment (either non-steroidal anti-inflammatory drugs or tumor necrosis factor-inhibitors) with an onset of heel pain ≥1 month prior to baseline.
The study was carried out in accordance with the principles of the Declaration of Helsinki, International Conference of Harmonisation Good Clinical Practice guidelines, and all applicable laws and regulations, with written informed consent obtained from all enrolled patients.
The MRI protocol of the study consisted of three mandatory sequences: T1-weighted Turbo Spin-Echo, T1-weighted Fast Spin-Echo, and T2-weighted short inversion time inversion-recovery [STIR] and predefined sequence parameters (details as reported previously) . MRIs were performed at 3 timepoints: screening, week 24, and week 52. No preparative drugs, contrast agents, or radionuclide agents were used. If both feet were affected, the foot with the highest pain level according to the patient’s decision was examined.
Heel enthesitis by MRI was assessed at screening by either the local radiologist or rheumatologist at the study site to determine the eligibility of the patient; the local rheumatologist was allowed to overrule the local radiologist’s assessment with respect to the positivity of the MR images. The MRI was positive for heel enthesitis if tendinitis with/without bursitis and/or BME with/without concomitant erosions in the insertional area of the Achilles tendon and/or the plantar aponeurosis was present. Based on the screening image, the investigator provided confirmation of whether a patient fulfills the inclusion criterion of MRI-positive heel enthesitis (yes/no) without a detailed evaluation of MRI parameters.
After inclusion in the study and independent of local assessment, the MR images were evaluated by two central readers in a consensus-read fashion. The readers were blinded for patient identification, site, timepoint, treatment, and clinical assessment and were experienced professionals with scientific and technical expertise in imaging modalities. Details of the central reading assessments have been reported previously . The initial MRI evaluation was performed based on PsAMRIS adapted to the heel with outcomes reported in the primary manuscript . The present report presents a post hoc analysis based on the re-evaluation of all MRIs by applying the recently developed HEMRIS.
HEMRIS was developed by OMERACT to assess enthesitis of the heel in patients with SpA . Inflammatory and structural parameters are each scored on a semi-quantitative scale of 0–3 (none to severe; detailed definitions for each severity grade can be found in the atlas of the OMERACT HEMRIS) . The total entheseal inflammation score is the sum of all inflammatory parameter scores in the area of the Achilles tendon, namely intra-tendon hypersignal, peri-tendon hypersignal, retrocalcaneal bursitis, and BME, thus ranging from 0 to 12. Similarly, the total entheseal inflammation score in the area of the plantar fascia is the sum of intra-aponeurosis hypersignal, peri-aponeurosis hypersignal, and BME (without bursitis), ranging from 0 to 9. The total structural damage score is the sum of all structural parameters scores, namely tendon thickening/aponeurosis thickening, bone spur, and bone erosion, ranging from 0 to 9 in each of the locations.
Categorical variables (qualitative and quantitative imaging parameters) were presented as descriptive summary statistics. Summaries included relative and absolute frequencies for each category. Continuous variables (MRI scores) were presented as mean with standard deviation (SD). From baseline to week 24, MRI data were missing for 14 patients due to study discontinuation, for 5 subjects although they completed week 24, and for 4 patients the MRIs were excluded from the analysis as they were assessed outside the visit window. From baseline to week 52, additional MRIs of 31 patients were missing due to study discontinuation, missed assessment, or were outside the visit window.
A chi-square analysis was performed to investigate potential associations of the inflammatory imaging parameters in the area of the Achilles tendon (intra-tendon hypersignal, peri-tendon hypersignal, bursitis, and BME) with clinical parameters directly related to the heel (Achilles tendon enthesitis as assessed by LEI, heel pain, and heel enthesopathy, as reported by patients). Changes in imaging and clinical parameter from screening to week 24 were categorized as either “improvement” or “no-improvement” to calculate P values.
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