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Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. Their clinical efficacy is well-documented, but the side effects associated with their use are still under investigation. These drugs cause several immune-related adverse events (ir-AEs), some of which stand within the field of rheumatology. Herein, we present a literature review performed in an effort to evaluate all publicly available clinical data regarding rheumatic manifestations associated with ICIs. The most common musculoskeletal ir-AEs are inflammatory arthritis, polymyalgia rheumatica and myositis. Non-musculoskeletal rheumatic manifestations are less frequent, with the most prominent being sicca, vasculitides and sarcoidosis. Cases of systemic lupus erythematosus or scleroderma are extremely rare. The majority of musculoskeletal ir-AEs are of mild/moderate severity and can be managed with steroids with no need for ICI discontinuation. In severe cases, more intense immunosuppressive therapy and permanent ICI discontinuation may be employed. Oncologists should periodically screen patients receiving ICIs for new-onset inflammatory musculoskeletal complaints and seek a rheumatology consultation in cases of persisting symptoms.

Background: To determine the conversion and reversion rates of tuberculosis (TB) screening tests (Tuberculin Skin Test-TST, Interferon Gamma Release Assay-IGRA: T-SPOT.TB) during biologic treatment in patients with rheumatic diseases and negative baseline screening.Methods: This was a long-term, longitudinal cohort study of 50 patients with rheumatic diseases and negative baseline TB screening (TST: < 5 mm, negative T-SPOT.TB) treated with tumor necrosis factor inhibitors (TNFi) or other non-TNFi biologics. Patients were rescreened at a mean time of 1.4 (first rescreening) and 6.9 (second rescreening) years from baseline, with both assays. The conversion (negative to positive) and reversion (positive to negative) rate was calculated for each TB screening test.Results: Fifty patients (mean age = 60 years) with various rheumatic diseases (rheumatoid arthritis: n = 24, spondyloarthropathies: n = 23, other: n = 3) were enrolled. During the first phase (baseline to first rescreening), all patients were treated with TNFi while during the second phase (first to second rescreening), TNFi (54%) and non-TNFi (46%) were used. Fifteen patients (30%) displayed conversion of at least 1 screening assay during follow-up (10 at the first and 5 at the second rescreening). This conversion rate was higher with TST (n = 11, 22% or 3.47/100 patient-years) compared to T-SPOT.TB (n = 4, 8% or 1.74/100 patient-years). Among the 10 converters at the first rescreening, 5 received isoniazid (INH) preventive therapy and 5 did not; an equal number of patients (3/5, 60%) reverted to negative with or without INH therapy. None of the patients developed active TB during follow-up (6.9 ± 1.0 years).Conclusions: Approximately one-third of patients with rheumatic diseases and negative baseline TB screening developed conversion of at least 1 screening test during long-term biologic treatment. This occurred most often with TST and was usually a transient event. These findings do not support routine serial TB retesting in biologic-treated patients with rheumatic diseases in the absence of TB risk factors.

Objectives Rituximab (RTX) use in the treatment of RA can be complicated by decrease in IgG, IgM or IgA levels (hypogammaglobulinemia-HGG). The aim of this study was to define the frequency of HGG in RA patients treated with RTX and to identify associations between its occurrence and patients’ characteristics, disease outcomes and serious infections rate. Methods RA patients treated with RTX in two rheumatology centers from January 2007 to January 2020 were retrospectively examined. Demographical, clinical and laboratory parameters were recorded at baseline and at last visit. Results Eighty-three patients (84.3% females) with a mean age of 63.2 years were enrolled. They had baseline DAS28(CRP) of 5.2  (1.1) and received a median (range) of 8 (2–20) RTX cycles. A total of 43.4%, 24.1% and 31.3% developed ‘any HGG’, ‘low IgG’ and ‘low IgM’, respectively. Lower baseline IgG and IgM levels were predictors of ‘low IgG’ and ‘low IgM’ occurrence, respectively. Patients who developed ‘low IgM’ exhibited lower DAS28(CRP) and increased rates of remission and low disease activity compared with those with normal IgM levels. Patients who maintained normal IgG were receiving methotrexate more frequently. No differences were observed in serious infections rate among subgroups. Conclusion HGG occurred in 43% of RTX-treated patients. Patients who developed low IgG or low IgM had lower baseline levels than those who did not. Concomitant DMARD and corticosteroid therapy was not associated with HGG. Low IgM, but not low IgG, development was associated with better disease outcomes. HGG was not associated with an increased incidence of serious infections.

Background: Real world evidence data regarding secukinumab (SEC) use in biologic-experienced patients with psoriatic arthritis (PsA) are scarce. Objectives:To assess the real life survival, safety and efficacy of SEC in biologic-experienced patients with PsA.Methods: All biologic-experienced PsA patients treated with SEC in 2 University Rheumatology Units were included (3/2016-12/2018). Patients' and disease characteristics were recorded at baseline and during SEC therapy.Results: 75 patients were included; 76% were females with a mean age of 53.9 years, median disease duration of 6.7 years and median SEC treatment duration of 11.1 months. At baseline, 97% had peripheral arthritis, 42% axial involvement, 22% enthesitis, and 12% dactylitis. Regarding previous biologic exposure, 48 (64%) had been exposed to anti-tumor necrosis factor (TNF) agents only, 5 (7%) to the interleukin (IL)-12/23 inhibitor (Ustekinumab-UST) only while 22 (29%) both to anti-TNFs and UST. Fifty-three percent received SEC in combination with non-biologics and 35% with glucocorticoids, respectively. During follow-up, statistically significant improvement in different disease activity indices were noted (DAS28-CRP, DAPSA, BASDAI). SEC survival rate at the end of follow-up was 64% (48/75), without difference between patients exposed to anti-TNFs only (67%) vs. anti-TNFs and UST (68%) as well as to 1 vs. ≥2 anti-TNFs. The rate of serious adverse events and serious infections during follow-up was 4.8 and 1.2/100 patient-years, respectively.Discussion: In real life, in biologic-experienced patients with PsA, SEC displayed a high retention rate, regardless of the type, and number of previous biologics (anti-TNFs ± anti-IL12/23), without significant side effects.

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Evidence suggests that serotonin is an inhibitor of bone formation. We aimed to assess: 1) serum serotonin levels in patients with ankylosing spondylitis (AS), a prototype bone-forming disease, compared with patients with rheumatoid arthritis (RA) and healthy subjects; 2) the effect(s) of TNFα blockers on serum serotonin levels in patients with AS and RA; and 3) the effect(s) of serum of AS patients on serotonin signaling. Serum serotonin levels were measured in 47 patients with AS, 28 patients with RA, and 40 healthy subjects by radioimmunoassay; t test was used to assess differences between groups. The effect of serum on serotonin signaling was assessed using the human osteoblastic cell line Saos2, evaluating levels of phospho-CREB by Western immunoblots. Serotonin serum levels were significantly lower in patients with AS compared with healthy subjects (mean ± SEM ng/mL 122.9 ± 11.6 versus 177.4 ± 24.58, p = 0.038) and patients with RA (mean ± SEM ng/mL 244.8 ± 37.5, p = 0.0004). Patients with AS receiving TNFα blockers had significantly lower serotonin levels compared with patients with AS not on such treatment (mean ± SEM ng/mL 95.8 ± 14.9 versus 149.2 ± 16.0, p = 0.019). Serotonin serum levels were inversely correlated with pCREB induction in osteoblast-like Saos-2 cells. Serotonin levels are low in patients with AS and decrease even further during anti-TNFα treatment. Differences in serotonin levels are shown to have a functional impact on osteoblast-like Saos-2 cells. Therefore, serotonin may be involved in new bone formation in AS.