PLACEBO-CONTROLLED EFFICACY AND SAFETY OF UPADACITINIB THROUGH ONE YEAR IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

BackgroundUpadacitinib (UPA), a Janus kinase inhibitor, was effective and well tolerated in patients (pts) with non-radiographic axial spondyloarthritis (nr-axSpA) through 14 weeks (wks) of treatment.[1]ObjectivesThis analysis assessed the efficacy and safety of UPA vs placebo (PBO) through 1 year.MethodsThe SELECT-AXIS 2 nr-axSpA study included a 52-wk randomized, double-blind, PBO-controlled period. Enrolled adults had a clinical diagnosis of active nr-axSpA fulfilling the 2009 ASAS classification criteria, objective signs of inflammation based on MRI sacroiliitis and/or elevated C-reactive protein, and an inadequate response to NSAIDs. One-third of pts had an inadequate response to biologic DMARDs. Pts were randomized 1:1 to UPA 15 mg once daily or PBO. Concomitant medications, including NSAIDs, had to be kept stable through wk 52. The study protocol outlined that pts who did not achieve ASAS20 at any two consecutive study visits between wks 24 to 52 should receive rescue therapy with NSAIDs, corticosteroids, conventional synthetic/biologic DMARDs, or analgesics. Cochran-Mantel-Haenszel (CMH) test with non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle missing data and intercurrent events for binary efficacy endpoints. Mixed-effect model repeated measures (MMRM) was used to assess continuous efficacy endpoints. NRI was used for binary endpoints after rescue and as observed analysis excluding data after rescue for continuous endpoints. Treatment-emergent adverse events (TEAEs) are reported through wk 52.ResultsOf the 314 pts randomized, 259 (82%;UPA, n=130;PBO, n=129) completed wk 52 on study drug. More pts achieved an ASAS40 response with UPA vs PBO from wks 14 to 52 with a 20% treatment difference at wk 52 (63% vs 43%;nominal P <.001;Figure 1). The proportion of pts achieving ASDAS inactive disease with UPA remained higher than PBO at wk 52 (33% vs 11%;nominal P <.0001;Figure 1). Consistent improvements and maintenance of efficacy were also seen across other disease activity measures. Between wks 24 and 52, fewer pts on UPA (9%) than PBO (17%) received rescue therapy. A similar proportion of pts in each treatment group had a TEAE (Table 1). Infections were the most common TEAE;the rates of serious infections and herpes zoster were higher with UPA vs PBO, although no new serious infections were reported from wks 14 to 52. COVID-19 events were balanced between treatment groups. No opportunistic infections, malignancy excluding non-melanoma skin cancer, adjudicated major adverse cardiovascular events, inflammatory bowel disease, or deaths were reported. Two pts (1.3%) on PBO had adjudicated venous thromboembolic events.ConclusionUPA showed consistent improvement and maintenance of efficacy vs PBO through 1 year across multiple disease activity measures. No new safety risks were identified with longer-term UPA exposure. These results continue to support the benefit of UPA in pts with active nr-axSpA.Reference[1]Deodhar A, et al. Lancet. 2022;400(10349):369–379.Table 1.Safety through week 52Event, n (%)PBO (n = 157)UPA 15 mg QD (n = 156)Any AE103 (66%)107 (69%)Serious AE6 (3.8%)6 (3.8%)AE leading to D/C4 (2.5%)6 (3.8%)COVID-19-related AE22 (14%)24 (15%)Deaths00Infection60 (38%)68 (44%) Serious infection1 (0.6%)2 (1.3%) Herpes zoster1 (0.6%)5 (3.2%)Malignancy other than NMSC00NMSC1 (0.6%)0Hepatic disorder7 (4.5%)6 (3.8%)Neutropenia1 (0.6%)8 (5.1%)MACE (adjudicated)00VTE (adjudicated)2 (1.3%)a0Uveitisb3 (1.9%)2 (1.3%)Inflammatory bowel disease00aBoth patients had non-serious events of deep vein thrombosis in the lower limb with risk factors including obesity and prior deep vein thrombosis in one patient and concomitant COVID-19 infection in the other patient.bThree events of uveitis occurred in each treatment group (among n = 3 patients in the PBO group and n = 2 patients in the UPA group);two events in the PBO group and one in the UPA group occurred in patients with a history of uveitis.AcknowledgementsAbbVie funded this study and participated in the study design, res arch, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsFilip van den Bosch Speakers bureau: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer., Walter P Maksymowych Consultant of: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis., Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB., Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie and Novartis, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Peter Wung Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.

Magnetic resonance imaging/ultrasound fusion-guided sacroiliac joint corticosteroid injection in patients with axial spondyloarthritis.

Local glucocorticoid injections are used in the treatment of isolated sacroiliitis in patients with spondyloarthritis. Sacroiliac joint injections can be performed intraarticularly or periarticularly. Since the accuracy of blind injections is low, fluoroscopy, magnetic resonance imaging, computed tomography, or ultrasonography guidance are used to increase the accuracy of sacroiliac joint injections. Currently, imaging fusion software is successfully used in sacroiliac joint interventions with three-dimensional anatomic information added to ultrasonography. Herein, we present two cases of sacroiliac joint corticosteroid injections under ultrasonography-magnetic resonance imaging fusion guidance.

What is Your Radiologic Diagnosis?: Journal of Pediatric Infection

Septic sacroiliitis is septic arthritis of the sacroiliac joints and is extremely rare. Since its clinical picture is not specific, imaging is integral to diagnosis. The patient, who had dyspnea and chest pain at the time of admission, had a body temperature of 39.2°C, showed bilateral subpleural multifocal ground-glass opacities in the thoracic CT performed in an external center, and findings consistent with perimyocarditis in cardiac magnetic resonance imaging (MRI) performed in our hospital. Cases of Pseudomonas aeroginosa have been documented in immunocompromised individuals or intravenous drug users, while cases of E. coli-associated septic sacroiliitis have been reported In patients with urinary tract Infections (5). Unilaterally Increased Involvement Is observed In septic sacroiliitis. Since the clinical picture Is not specific, especially In children at an early age, this can help determine the location of the pain (7).

A case of Candida albicans septic sacroiliitis complicating severe COVID-19 infection

Case report-IntroductionBacterial and fungal infections are recognised complications of viral pneumonia, particularly in patients who are critically ill. We describe a case of fungal sacroiliitis complicating severe COVID-19 pneumonia following a prolonged intensive care unit (ICU) admission.Candida albicans sacroilitis is a rarely reported infection with few case reports in the literature. Candida osteoarticular infections can present as septic arthritis, with knee involvement in 75% of cases, or osteomyelitis. The latter presentation differs based on age-vertebral involvement (51%) is more common in adults while children are more likely to present with infection in the long bones, ribs, or sternum.Case report-Case descriptionA 48-year-old Afro-Caribbean gentleman with a history of hypertension and obesity was admitted to the ICU with clinical, laboratory and radiographic features of COVID-19 infection despite persistently negative swabs. Whilst in ICU he required mechanical ventilation. His stay was further complicated by multiple infections, pulmonary emboli, and the presence of a cavitating lesion in the left lung. Cultures from bronchoalveolar lavage and a central venous catheter line grew Serratia Mascense, candida glabrata and pseudomonas were isolated from his urine. He was treated with multiple antibiotics including meropenem, tazocin, ceftazidime and avibactam.After 61 days in the ICU he was transferred to the ward. He developed severe pain in his right hip which was worse on movement. This was followed by urinary incontinence and sensory deficit in the right L2/L3 dermatome. He underwent magnetic resonance imaging (MRI) of his spine and sacroiliac joints which showed right sided sacroiliitis and oedema around the iliopsoas muscle. He was started on vancomycin, later changed to ceftazidime avibactam and metronidazole. An echocardiogram did not show any vegetations. He underwent a biopsy of his sacroiliac joints which confirmed the presence of leucocytes, extended cultures yielded candida albicans in one out of two biopsy specimens.Considering ongoing pyrexia, pain and inflammatory markers, intravenous fluconazole was added to his antibiotic regimen which resulted in a marked improvement in mobility. After four weeks, ceftazidime, metronidazole and avibactam were stopped, and fluconazole was administered as oral tablets. 6 days later he became febrile and IV fluconazole was restarted.A repeat chest CT showed resolution of the cavity but ongoing changes suggestive of organising pneumonia. A repeat MRI of the sacroiliac joints revealed minor improvement. Intravenous Fluconazole was continued for a total of 8 weeks and was changed to tablets for complete a total of 12 weeks.Case report-DiscussionThis is a severe case of COVID-19 infection who despite 9 negative PCR tests, on day 53, had positive IgG for SARS-CoV-2 infection, confirming our clinical suspicion. Particularly in the ICU setting, individuals are approximately ten times more likely to have secondary bacterial/fungal infections with more frequent detection of multidrug-resistant Gram-negative pathogens.This case highlights several difficulties. Urine cultures had confirmed candida albicans, likely to be related to catheter related urinary tract infections, and a possible source for our patient but also a resistant pseudomonas aeruginosa species. Furthermore, cultures were positive for Serratia Mascense, candida glabrata. He had also already been treated with prolonged, broad spectrum antimicrobial treatment. Considering this, establishing the aetiology of the septic sacroiliitis was challenging. The rarity of candida sacroiliitis and presence of the organism in just one specimen made this more difficult. This led to the decision of a repeat sacroiliac biopsy to supply sufficient samples for further microbial analyses such as 16S, 18S and mycobacteria culture, all of which were negative.He became febrile after the discontinuation of antimicrobials and a switch to oral fluconazole therapy. He was extensively re-investigated and despite resolution of t e lung cavity, there were changes which could have been consistent with an organising pneumonia. At this point he was neutropenic, mildly eosinophilic, and therefore a drug reaction was also considered.Repeat MRI revealed resolving muscle inflammation and minimal change at the bone site, with erosions and possible reactive bone marrow oedema. Following discussion with microbiology the decision was made to persist with intravenous Fluconazole. He continued to improve, and his inflammatory markers normalised after 8 weeks of treatment. Prednisolone was started for COVID-19 related pneumonitis. Long-term antifungal treatment is advisable, and we aim to complete 12 weeks of treatment.Case report-Key learning points Patients with SARS-CoV-2 infection, particularly those requiring ICU admission were at risk of developing superinfections with multidrug-resistant Gram-negative bacteria or fungal infections.Candida albicans sacroiliitis is rare therefore early aspiration/biopsy is essential for the management.Longer treatment is needed in osteoarticular candida infections, even up to 6 or 12 months, therefor long-term close monitoring of this patients is essential.The utility and timing of reimaging patients following such infections is still unclearClose multidisciplinary and interdisciplinary team collaboration is essential in the management of this complex patients.

A rare case of anti-tnf induced panniculitis

Case report-IntroductionPanniculitides comprise a heterogeneous group of inflammatory diseases involving the subcutaneous fat. They remain the most challenging areas for clinicians. Skin biopsy is commonly needed to confirm diagnosis. Because there are many underlying aetiologies for panniculitis, detailed history and thorough investigations are needed. We present a case of A 20-year male who was admitted with painful lumps treated initially as cellulitis/abscess but turned to be neutrophilic panniculitis on skin biopsy. Extensive workup failed to reveal underlying aetiology. Eventually Imradli (AntiTNF) was thought to be the culprit and therefore was kept on hold with no recurrence of panniculitis.Case report-Case descriptionA 20-year-old, Asian Malawian. Moved to the UK at the age of 6. He was diagnosed with Ankylosing spondylitis in November 2016. Initially received Naproxen followed by (Humira) with good clinical response. He was switched to biosimilar Imradli in Nov 2019. He was admitted with 2-3 weeks history of progressive right hip and buttock pain, 1 week of very tender erythematous swelling of the right buttock but without fever or weight loss. He reported mild weakness of lower limbs. Physical examination revealed 5x 8 cm swelling on Right buttock, Rest of examination was unremarkable. He was reviewed by neurology team who arranged MRI spine and brain, EMG and lumbar puncture which all came back as unremarkable excluding the possibilities of myelitis and myositis. Initially thought to be abscess/cellulitis but absence of fever/inflammatory response, abnormal CT finding and no response to antibiotics made it less likely. While the Right buttock erythema/swelling started to resolve, he developed two new migratory erythematous lesions appearing around the left buttock and lower lumbar spine. Working diagnosis of panniculitis was made which was confirmed on biopsy. Due to lack of response to NSAIDs, colchicine or oral steroids, a 3rd biopsy of the freshest lesion was performed to exclude deep-seated infection.Investigations-FBC, U&ES, LFT, CRP, CK, ACE-all were unremarkableASO titre <200, serology for Borrelia and TPHA negative.Viral, parasitic, and Autoimmune screen were unremarkable.CXR clear, MRI/CT: extensive subcutaneous inflammatory changes in the right buttock with sacral oedema.PET-CT-showed resolving inflammatory changes in the right flank, FDG intake in C6 and SI joints presumed secondary to ankylosing spondylitis and sacroiliitis.The underlying cause of panniculitis remains uncertain. Anti TNF was kept on hold and the patient was followed up with no evidence of recurrence of panniculitisCase report-DiscussionPanniculitis (inflammation of subcutaneous fat) is a relatively uncommon condition. It has various aetiologies including infection, trauma, inflammation, and malignancy. Skin biopsy can give valuable information including microbiological studies if infectious panniculitis was suspected. However, clinical correlation and careful consideration of the differential diagnosis is needed in many cases.The diagnosis can be quite challenging as in this case where all investigations and skin biopsy could not point towards the underlying aetiology. Although anti-TNF inhibitors are commonly used in treating a wide range of autoimmune conditions. But their use can lead to the development of secondary autoimmune diseases, such as cutaneous vasculitis, lupus-like syndrome, and interstitial lung disease, paradoxically induced by anti-TNF-a agents. Llamas-Velasco and Requena, reported the first case of panniculitis induced by etanercept injection in a 62-year-old woman with severe psoriasis who developed an erythematous, slightly painful nodule on the skin of the anterior abdominal wall.Adalimumab induced lupus panniculitis was reported in a Rhu-lupus patient. Although the lesions stopped progressing after cessation of adalimumab, they remained unchanged for two more years. The mechanism for adalimumab-induced CLE is uncertain.Although there is not enough data about autoimmunity with biosimilars, we think seco dary autoimmune conditions could similarly be induced by biosimilar as illustrated in this case. Anti-TNF induced cutaneous panniculitis is considered most likely although uncertain. If anti-TNF drug-induced, this should gradually resolve but can be slow (4-6 months). Corticosteroids have been added for an anti-inflammatory response, but there was little benefit which might point to a different pathogenetic mechanism.NSAIDs has helped to keep his AS relatively stable during the COVID-19pandemic. During the last review, the patient expressed his wishes to go back on biologic. But the question remains whether he will a have a recurrence of panniculitis or not?Case report-Key learning points1/Anti-TNF inhibitors sometimes cause secondary autoimmune conditions like cutaneous vasculitis, lupus-like syndrome, but there is not enough data regarding biosimilar induced autoimmunity.2/This case illustrates the high importance of having a tissue diagnosis. (whenever there is an issue, the diagnosis would be in the tissue).3/There is still uncertainty whether a recurrence of panniculitis might occur or not if the patient went again on biologics.

Evidence for the Use of Secukinumab in Patients with Radiographic and Non-radiographic Axial Spondyloarthritis in the Last 5 Years.

Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disorder that causes chronic pain, primarily in the spine and sacroiliac joints. It is characterized by the presence of type 1 major histocompatibility complex HLA-B27 genetic marker, arthritis in peripheral joints, enthesitis and/or dactylitis and extra-articular manifestations. Current guidelines recommend biological therapy when first-line therapy is not sufficiently effective. The finding that the interleukin (IL)-17 axis is vital for the pathogenesis of axSpA propelled the development of secukinumab, a fully human monoclonal antibody directed against IL-17A. The present review provides evidence on the efficacy and safety of secukinumab in the treatment of radiographic and non-radiographic axSpA from nine randomized controlled phase III trials, as well as evidence from real-world observational analyses. The primary endpoint in six clinical trials was the proportion of patients meeting the Assessment of SpondyloArthritis international Society criteria for either 20% or 40% improvement (ASAS20, ASAS40) at week 16. Significantly more patients achieved the primary endpoint with secukinumab compared with placebo in all the studies except MEASURE 4. Both clinical trials and real-world studies showed significant improvements in the secondary endpoints of disease activity, quality of life, and pain and fatigue relative to placebo. The benefits of secukinumab were generally sustained during longer-term (up to 5 years) treatment. Overall, secukinumab was well tolerated with a low frequency of adverse events and treatment persistence was high in the real-world setting. Although indirect comparisons suggest that secukinumab and adalimumab have comparable efficacy and safety, they are being directly compared in the ongoing SURPASS study. During the current coronavirus disease 2019 (COVID-19) pandemic, it is advisable to continue biological therapy in patients who do not have severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, but interrupt treatment during an infection, reinitiating once the patient has recovered from the infection. In conclusion, secukinumab is a largely safe and effective treatment for radiographic and non-radiographic axSpA.

Post-COVID-19 Arthritis and Sacroiliitis: Natural History with Longitudinal Magnetic Resonance Imaging Study in Two Cases and Review of the Literature.

Severe acute respiratory coronavirus-2 syndrome (SARS-CoV-2) is a well-known pandemic infectious disease caused by an RNA virus belonging to the coronaviridae family. The most important involvement during the acute phase of infection concerns the respiratory tract and may be fatal. However, COVID-19 may become a systemic disease with a wide spectrum of manifestations. Herein, we report the natural history of sacroiliac inflammatory involvement in two females who developed COVID-19 infection with mild flu-like symptoms. After the infection they reported inflammatory back pain, with magnetic resonance imaging (MRI) studies showing typical aspects of sacroiliitis. Symptoms improved with NSAIDs therapy over the following months while MRI remained positive. A literature review was performed on this emerging topic. To our knowledge, this is the first MRI longitudinal study of post-COVID-19 sacroiliitis with almost one year of follow-up. Predisposing factors for the development of articular involvement are unclear but a long-lasting persistence of the virus, demonstrated by nasopharyngeal swab, may enhance the probability of altering the immune system in a favourable background.

Method for Diagnosing the Bone Marrow Edema of Sacroiliac Joint in Patients with Axial Spondyloarthritis Using Magnetic Resonance Image Analysis Based on Deep Learning.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease of the sacroiliac joints. In this study, we develop a method for detecting bone marrow edema by magnetic resonance (MR) imaging of the sacroiliac joints and a deep-learning network. A total of 815 MR images of the sacroiliac joints were obtained from 60 patients diagnosed with axSpA and 19 healthy subjects. Gadolinium-enhanced fat-suppressed T1-weighted oblique coronal images were used for deep learning. Active sacroiliitis was defined as bone marrow edema, and the following processes were performed: setting the region of interest (ROI) and normalizing it to a size suitable for input to a deep-learning network, determining bone marrow edema using a convolutional-neural-network-based deep-learning network for individual MR images, and determining sacroiliac arthritis in subject examinations based on the classification results of individual MR images. About 70% of the patients and normal subjects were randomly selected for the training dataset, and the remaining 30% formed the test dataset. This process was repeated five times to calculate the average classification rate of the five-fold sets. The gradient-weighted class activation mapping method was used to validate the classification results. In the performance analysis of the ResNet18-based classification network for individual MR images, use of the ROI showed excellent detection performance of bone marrow edema with 93.55 ± 2.19% accuracy, 92.87 ± 1.27% recall, and 94.69 ± 3.03% precision. The overall performance was additionally improved using a median filter to reflect the context information. Finally, active sacroiliitis was diagnosed in individual subjects with 96.06 ± 2.83% accuracy, 100% recall, and 94.84 ± 3.73% precision. This is a pilot study to diagnose bone marrow edema by deep learning based on MR images, and the results suggest that MR analysis using deep learning can be a useful complementary means for clinicians to diagnose bone marrow edema.