Showing papers by "Dimitrios Daoussis published in 2021"

Immune checkpoint inhibitor-induced musculoskeletal manifestations

Abstract: Immune checkpoint inhibitors (ICI) associate with a wide range of immune-related adverse events (Ir-AE), including musculoskeletal manifestations. We aimed at identifying all studies reporting musculoskeletal Ir-AE. An electronic (Medline, Scopus and Web of Science) search was performed using two sets of key words. The first set consisted of: arthritis, musculoskeletal, polymyalgia rheumatica and myositis. The second set consisted of: anti-PD-1, anti-PD-L1, anti-CTLA-4, ipilimumab, tremelimumab, pembrolizumab, nivolumab, atezolizumab, avelumab and durvalumab. We identified 3 prospective studies, 17 retrospective studies and 4 case series reporting 363 patients in total. Combined data from all three prospective studies provide a prevalence rate of 6.13%. Most patients were males (59.68%) and the vast majority (73%) were on programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors. Most studies report a median time of ≤ 12 weeks from first ICI administration to symptom onset. The main clinical phenotypes reported were: (a) inflammatory arthritis (57.57%), (b) myositis (14.04%) and (c) polymyalgia rheumatica (PMR) (12.12%). A total of 256 patients required steroids (70.52%) and 67 patients (18.45%) were treated with DMARDs. Positive auto-antibodies and family history of any autoimmune disease were present in 18.48% and 19.04% of cases, respectively. Only a few patients (19%) had to discontinue treatment due to musculoskeletal Ir-AE. Two prospective studies show that significantly more patients with musculoskeletal Ir-AE exhibit a favorable oncologic response compared to patients not exhibiting such manifestations whereas retrospective studies show that 77.22% of patients with musculoskeletal Ir-AE have a good tumor response. One out of 15 patients treated with ICI will develop musculoskeletal Ir-AE; in most cases the severity of these manifestations is mild/moderate and usually ICI may be continued. Rheumatologists should familiarize with this new clinical entity and develop relevant therapeutic algorithms.

Real-world safety and efficacy data of immunotherapy in patients with cancer and autoimmune disease: the experience of the Hellenic Cooperative Oncology Group

Abstract: Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited. We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS). Among 123 patients with pre-existing AID who received ICI, the majority had been diagnosed with non-small cell lung cancer (NSCLC, 68.3%) and melanoma (14.6%). Most patients had a rheumatologic (43.9%), or an endocrine disorder (21.1%). Overall, 74 (60.2%) patients experienced an immune-related adverse event (irAE) after ICI initiation, AID flare (25.2%), or new irAE (35%). Frequent irAEs included thyroiditis, dermatitis and colitis. ICI was permanently discontinued due to unacceptable (8.1%) or fatal (0.8%) toxicity. In patients with NSCLC, corticosteroid treatment at the initiation of immunotherapy was associated with poor PFS (HR = 2.78, 95% CI 1.40–5.50, p = 0.003). The occurrence of irAE was associated with increased PFS (HR = 0.48, 95% CI 0.25–0.92, p = 0.026). Both parameters maintained their independent prognostic significance. ICI in patients with cancer and pre-existing AID is associated with manageable toxicity that infrequently requires treatment discontinuation. However, since severe AID flare might occur, expected ICI efficacy and toxicity must be balanced. NCT04805099

Protracted severe COVID-19 pneumonia following rituximab treatment: caution needed.

Abstract: The outcomes of COVID-19 in patients treated with biologic agents are a subject of intense investigation. Recent data indicated that patients under rituximab (RTX) may carry an increased risk of serious disease. We performed an electronic search in Medline and Scopus using the keywords rituximab and COVID-19. We present a rare case of severe, protracted COVID-19 pneumonia in a patient with mixed connective tissue disease (MCTD) who was infected a few days following RTX treatment. In a relevant literature search, we identified 18 cases of patients with rheumatic diseases (6 RA, 8 ANCA vasculitis, 3 systemic sclerosis and 1 polymyositis) treated with RTX who experienced an atypical and/or prolonged course of COVID-19 pneumonia with no evidence of cytokine storm. Our case indicates that RTX may unfavorably affect outcomes following SARS-CoV-2 infection. B cell depletion may dampen the humoral response against the virus; we may hypothesize that B cell-depleted patients may be protected from cytokine storm but on the other hand may have difficulties in virus clearance leading to a protracted course. Taking into account that COVID-19 vaccines are available we may consider delaying RTX infusions at least in patients without life threatening disease, until vaccination is completed.

B cells in systemic sclerosis: from pathophysiology to treatment.

Abstract: Systemic sclerosis is a debilitating autoimmune disease with unknown pathogenesis. The clinical phenotype of fibrosis is preceded by vascular and immunologic aberrations. Adaptive immunity has been extensively studied in patients with the disease and B cells appear to be dysregulated. This is evident in peripheral blood B cell subsets, with activated effector B cells and impaired B regulatory function. In addition, B cells infiltrate target organs and tissues of patients with the disease, such as the skin and the lung, indicating a probable role in the pathogenesis. Impaired B cell homeostasis explains the rationale behind B cell therapeutic targeting. Indeed, several studies in recent years have shown that depletion of B cells appears to be a promising treatment alongside current established therapeutic choices, such as mycophenolate. In this review, B cell aberrations in animal models and human patients with systemic sclerosis will be presented. Moreover, we will also summarize current existing data regarding therapeutic targeting of the B cells in systemic sclerosis.

Renal dysfunction in systemic sclerosis beyond scleroderma renal crisis.

Abstract: Research regarding renal involvement in SSc has almost exclusively focused on scleroderma renal crisis (SRC). There are relatively limited data regarding renal impairment in SSc beyond SRC. We performed an electronic search using the key words systemic sclerosis or scleroderma combined with each of the following: renal dysfunction, kidney, glomerular filtration rate (GFR), proteinuria and hematuria. We searched for reports relevant to renal dysfunction in SSc beyond SRC. In 796 SSc patients recruited in five studies. 251 (31.5%) had GFR < 90 ml/min whereas 155(19.5%) patients had GFR < 60 ml/min. Most data indicate that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula should be considered as the most suitable tool for assessing renal function in SSc pts, since it provides similar results to measured GFR. These data indicate that renal dysfunction in SSc in not uncommon and therefore patients with SSc should have their renal function assessed by GFR estimation on a regular basis.

Systemic Sclerosis Associated Acro-osteolysis and Tumor Necrosis Factor Blockade.

Abstract: FIGURE. Plain posteroanterior radiograph of both hands. There is osteolysis of both ulnar heads more pronounced on the left (black arrows). The radiocarpal, intercarpal, and carpometacarpal joints are ankylosed with obliteration and sclerosis of the intra-articular spaces. There is diffuse osteopenia. A 64-year old white woman was first seen in February 2019 as an inpatient in our hospital suffering from a respiratory tract infection. The patient was diagnosed with systemic sclerosis (SSc) in 2003 based on Raynaud phenomenon, skin thickening/ sclerodactyly, arthritis of wrists/small joints of the hands, and positive anti-Scl70 antibodies. She was initially treated with 15 mg of methotrexate and low-dose steroids. Following a few months, etanercept (50 mg weekly) was added to control her joint manifestations. Treatment with methotrexate and etanercept was maintained up until her hospital admission, without interruption, whereas low-dose steroids were also used intermittently, according to her symptoms.Whenwe saw her, she had a typical SSc phenotype (scleroderma face, skin atrophy, sclerodactyly with claw hands and pitting scars), and her chest radiograph showed clear evidence of interstitial lung disease. Laboratory workup revealed positive rheumatoid factor and anti-Scl70 antibodies. A radiograph of her hands showed advanced acro-osteolysis of both ulnar heads as well as fusion and sclerosis of carpal bones (Fig.). Pathogenesis of SSc-related acro-osteolysis is not well understood, but vascular and not inflammation-driven mechanisms seem to predominate. In this rare case, a powerful immunosuppressive regimen in the form of methotrexate and a tumor necrosis factor α blocker was administered throughout a period of more than 15 years and was completely ineffective in preventing the development of bone changes, especially acro-osteolysis. Our case illustrates that bone changes and acro-osteolysis in SSc are tightly linked to the underlying vasculopathy in sharp contrast to RA where erosions and bone loss are linked to tumor necrosis factor– driven inflammatory responses.

A Case Report of Favourable Response of Polymyositis to Methotrexate Monotherapy.

Abstract: INTRODUCTION Steroids constitute either the main treatment for some rheumatic diseases such as temporal arteritis or may be used as a bridging therapy in others, such as rheumatoid arthritis.1,2 The efficacy of steroids in rheumatic diseases is well documented but there was always a concern regarding their well-known side effects. Polymyositis is generally considered a severe rheumatic disease, and steroids are always used in high doses either as monotherapy or in combination with immunosuppressant agents. One of the most widely used drugs for polymyositis is methotrexate (MTX); other therapeutic options include azathioprine, mycophenolate mofetil, cyclosporine, or biologics such as rituximab.3,4 We report herein a rare case of polymyositis that responded favourably to MTX monotherapy without the use of steroids.