Secukinumab is not associated with cancer recurrence or progression in patients with spondyloarthritis and history of neoplastic disease.

Secukinumab is a monoclonal antibody directed against interleukin-17 approved for the treatment of psoriasis and spondyloarthritis. The favorable oncological profile of secukinumab in patients with a history of malignancy has been shown in patients with psoriasis. However, systematic data to this regard have not been published yet for patients with spondyloarthritis. The objective of the present study was to evaluate the oncological safety of secukinumab in patients affected by this group of diseases. We performed a retrospective study in which we identified from our cohort patients with spondyloarthritis treated with secukinumab and with a history of malignancy. These patients' baseline demographic, treatment, rheumatological, and oncological data were collected. The neoplastic outcome (i.e., cancer recurrence or progression) after secukinumab start was then analyzed. Our study included 22 patients with spondyloarthritis. The most frequently reported oncological diagnosis was breast cancer (9 [41%] patients). Secukinumab was started after a median of 24 months following cancer diagnosis. At this time point, all but three patients were in oncological remission. No case of cancer relapse or progression was recorded over a median follow-up of 30 months. In the largest cohort reported to date to this regard, secukinumab was not associated with oncological recurrence or progression in patients with spondyloarthritis with a history of malignancy. Secukinumab may, therefore, represent a safe option in this clinical scenario.

Autoantibody positivity predicts severity of rheumatic immune-related adverse events to immune-checkpoint inhibitors.

OBJECTIVE: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors are responsible for a considerable burden of morbidity and mortality. Predictors of severity of rheumatic irAEs have not been identified yet. The objective of this study was to test the hypothesis whether the presence of autoantibodies could be associated with a more severe and difficult-to-treat clinical phenotype of rheumatic irAEs. METHODS: Patients referred to our centre due to the onset of rheumatic irAEs were prospectively recruited between June 2018 and December 2020. A pre-specified panel of autoantibodies was tested in each patient at baseline visit. All patients were started on glucocorticoids and then followed-up. Conventional or biologic immunosuppressants were started in case of steroid-refractory or relapsing disease. Logistic regression analysis was performed to evaluate the association between the baseline positivity of at least one autoantibody and the necessity of an add-on therapy. RESULTS: Fourty-three patients with rheumatic irAEs were enrolled. Twenty-five (58%) patients had positivity of at least one of the tested autoantibodies. Twenty-two (51%) patients required the start of an additional immunosuppressant during follow-up. The only factor associated with the necessity of an add-on therapy was autoantibody positivity (OR=9.65, 95% CI:2.09-44.56; p-value 0.004). CONCLUSIONS: The presence of autoantibodies in patients with cancer who develop rheumatic irAEs could predict their progression to difficult-to-treat clinical manifestations. This finding might prompt a future therapeutic approach based on a tailored and earlier immunosuppressive treatment in selected cases.

Tocilizumab for the treatment of immune-related adverse events: a systematic literature review and a multicentre case series.

OBJECTIVE: Research is moving towards a more personalized management of immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI). Our objective was to evaluate the efficacy and safety of tocilizumab in the treatment of these clinical manifestations. METHODS: A systematic literature review was performed to retrieve data about the use of tocilizumab in the treatment of irAEs. Additionally, data from cancer patients referred to our Immune-related Adverse Event Clinic and treated with tocilizumab were collected. RESULTS: Our literature review identified 20 articles and 11 meeting abstracts. Data about 91 cancer patients who received tocilizumab for the treatment of irAEs were collected. In 85% of cases, this therapy was associated with clinical benefit and no case of disease progression was reported. ICI therapy was continued following irAE onset and biologic therapy initiation in only three patients. Five patients developed irAEs upon ICI initiation and were subsequently treated with tocilizumab at our Centre. At a median follow-up of eight months, tocilizumab was safely continued along with ICI in three out of five patients, and an adequate control of irAE was obtained in all cases. No significant adverse reactions to tocilizumab were reported. Only one patient experienced a disease progression 18 months after ICI discontinuation. CONCLUSION: Both our systematic literature review and case series highlight the efficacy and safety of tocilizumab in the treatment of irAEs. Furthermore, they both support the possibility of a combined approach with tocilizumab and ICI, to guarantee an effective irAEs management without losing the oncologic response.

Drug retention rates of biological agents in adult onset Still's disease.

OBJECTIVES: To assess drug retention rates (DRRs) and reasons for discontinuation of biologic disease-modifying antirheumatic drugs (bDMARDs) in a large monocentric cohort of patients with adult onset Still's disease (AOSD). METHODS: Clinical data of AOSD patients treated with at least one bDMARD and followed up at our Center were retrospectively evaluated. Data about disease duration, number of previous bDMARDs, concomitant treatments, and reasons for therapy discontinuation were collected. Survival curves were examined by the Kaplan-Meier method and compared using a stratified log-rank test. 24-month DRRs were calculated for each bDMARD. Hazard ratio (HR) for previous bDMARD use was evaluated. RESULTS: Forty-two AOSD patients received a total of 79 bDMARD-courses. Anakinra (ANK; n = 41) was the most frequently used bDMARD, followed by tocilizumab (TCZ; n = 21) and Tumor Necrosis Factor inhibitors (TNFi; n = 17). Biologic agents were administered concomitantly with prednisone in all cases (mean dose, 23 ± 18 mg/day) and with csDMARD therapy in 54 (68%) of courses. Thirty-six (46%) treatment courses were discontinued by 24 months. DRRs at 24 months were 62.5% for TCZ, 53.1% for ANK, and 11.8% for TNFi. ANK and TCZ DRRs were similar (p = 0.576), but significantly higher than TNFi (p = 0.015). Previous biologic therapies did not impact DRR (HR 0.73, 95% CI = 0.40 - 1.31, p = 0.288). CONCLUSIONS: In our AOSD study population, 24 months DRRs of TCZ and ANK were similar and significantly higher than the TNFi DRR. Previous use of biologic agents did not affect DRRs.

Obesity and its role in the management of rheumatoid and psoriatic arthritis.

In the last decade, interest has been growing in the relationship between obesity and several other clinical conditions, besides the well-established links between body mass index (BMI) and cardiovascular diseases or cancer. A particular focus has been put on the impact of a higher BMI on immune-mediated diseases such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Obesity has been found to be associated with greater arthritis activity and a reduced probability of response to anti-tumor necrosis factor (TNF) agents. On the other hand, weight loss increases the chances of treatment success. Although the direct effect of a higher body mass on drug clearance might in part account for this obesity-related effect, other biological mechanisms could be involved. The evidence of a negative influence of obesity on arthritis treatment is particularly strong as far as anti-TNF inhibition is concerned; on the contrary, the response to biologic agents targeting interleukin-6, cytotoxic T lymphocyte antigen 4, or CD20 seems not to be negatively affected by a higher BMI. In this review, we will consider the main studies investigating the influence of obesity on anti-rheumatic treatment in RA and PsA patients. We will also try to hypothesize about a possible pathogenic explanation of this phenomenon and its role in the choice of an appropriate and personalized therapy.

Repurposing of Biologic and Targeted Synthetic Anti-Rheumatic Drugs in COVID-19 and Hyper-Inflammation: A Comprehensive Review of Available and Emerging Evidence at the Peak of the Pandemic.

Coronavirus disease 2019 (COVID-19) is a condition caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe cases of COVID-19 result in acute respiratory distress syndrome and death. A detrimental, hyper-inflammatory immune response with excess release of cytokines is the main driver of disease development and of tissue damage in these patients. Thus, repurposing of biologic agents and other pharmacological inhibitors of cytokines used for the treatment of various inflammatory conditions emerged as a logical therapeutic strategy to quench inflammation and improve the clinical outcome of COVID-19 patients. Evaluated agents include the interleukin one receptor blocker anakinra, monoclonal antibodies inhibiting IL-6 tocilizumab and sarilumab, monoclonal antibodies inhibiting granulocyte-monocyte colony stimulating factor and tumor necrosis factor, and Janus kinase inhibitors. In this review, we discuss the efficacy and safety of these therapeutic options based on direct personal experience and on published evidence from observational studies and randomized clinical trials.