OP0335 A PROSPECTIVE CLINICAL AND MRI STUDY OF IMMUNE CHECKPOINT INHIBITOR (ICI)-INDUCED MUSCULOSKELETAL MANIFESTATIONS MYO-FASCIITIS AND NOT SYNOVITIS IS THE PROMINENT IMAGING FINDING
Authors: Dimitrios Daoussis, Alexandra Filippopoulou, Pantelis Kraniotis, Spyridoula Theodoraki, Rafaella Argiriadi, Thomas Makatsoris, Angelos Koutras, Aikaterini Solomou, Haralampos Kalofonos, Stamatis-Nick Liossis
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Immune check point inhibitors (ICI) were a breakthrough in cancer therapeutics. These agents target certain "brakes" of the immune system aiming at activating T cells to fight cancer. Taking into account their mechanism of action it is no surprise that they have been associated with immune related adverse events <h3>Objectives</h3> To assess the prevalence, clinical and imaging characteristics of ICI-induced musculoskeletal manifestations in a prospective manner <h3>Methods</h3> This is a prospective, clinical and MRI study conducted from Jan 2016 to Oct 2018. All patients treated with ICI who developed musculoskeletal manifestations were referred to the Rheumatology Department and subjected to a full clinical assessment and laboratory workup. An MRI of the involved area(s) was performed within one week of the initial clinical evaluation. In 2 patients MRI was not performed due to claustrophobia (n=1) and presence of non compatible metal implant (n=1). <h3>Results</h3> During the study period a total of 130 patients were treated with ICI. Of those, 10 (7.7%) developed ICI-induced musculoskeletal manifestations. They suffered from lung (n=4), bladder (n=3), renal cancer (n=2) or melanoma (n=1) and received treatment with nivolumab (n=7), pembrolizumab (n=1), durvalumab (n=1) and atezolizumab (n=1). They were mostly male (n=8) with a mean ± SEM age of 66.7 ± 2.6 years. The median (range) time from ICI treatment since development of symptoms was 2.5 (1-22) months. Autoantibodies (RF/ACPA/ANA) were negative in all patients and only 3/10 had a mild/moderate increase of inflammatory markers at disease onset. Three different patterns of musculoskeletal manifestations were found: i) Prominent joint involvement (n=3). Areas involved were the small joints of the hands (n=2) and knee/ankle (n=1). The MRI of the latter patient depicted not only synovitis but also myositis of the muscles surrounding the involved joints, ii) Prominent "periarticular" involvement (n=4). These patients had diffuse swelling of the hands (n=4) feet (n=3) or knees (n=1). Joints retained a good and relatively painless range of motion. MRI depicted mild synovitis with more prominent myositis and/or fasciitis in the surrounding tissues in all cases, iii) Myo-fasciitis (n=3). In all 3 such cases the involved area was the knee. Clinically, these patients presented with pain in the knee and either no objective signs of arthritis (n=2) or swelling with non inflammatory synovial fluid. MRI depicted myo-fasciitis of the surrounding muscles in all cases; a partial tear of the quadriceps tendon was also found in the patient with knee swelling. Overall, symptoms were mild/moderate and responded well to treatment (low dose steroids in 6 and NSAIDs/analgesics in 4) with no need for ICI discontinuation. <h3>Conclusion</h3> In our cohort ICI-induced musculoskeletal manifestations were not uncommon and developed in 7.7% of patients. Imaging evidence of myo-fasciitis was found in all patients indicating that the muscle/fascia is more frequently involved than the synovium. Our clinical and imaging data point to the direction that ICI-induced musculoskeletal manifestations mostly involve periarticular structures and associate mainly with myo-fasciitis and not synovium based pathology <h3>Disclosure of Interests</h3> None declared