Incidence Of Serious Infections Research Articles

Interleukin-1 blockade with anakinra and heart failure following ST-segment elevation myocardial infarction: results from a pooled analysis of the VCUART clinical trials.

ST-segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). In this study, we sought to evaluate the effect of anakinra, a recombinant interleukin-1 receptor antagonist, on the incidence of HF. We performed a pooled analysis of three early phase randomized clinical trials. The endpoints included the composite of all-cause death and new-onset HF, and the composite of all-cause death and hospitalization for HF at 1-year follow-up. Safety events, including injection site reaction and serious infections, were also recorded. We analysed 139 patients with STEMI from three separate trials: VCUART (N=10), VCUART2 (N=30), and VCUART3 (N=99). Of these, 84 (60%) patients were randomized to anakinra and 55 (40%) to placebo. Treatment with anakinra significantly reduced the incidence of all-cause death or new-onset HF (7 [8.2%] vs. 16 [29.1%], log-rank P=0.002) and of all-cause death or HF hospitalization (0 [0] vs. 5 [9.1%], log-rank P=0.007). Patients treated with anakinra had significantly higher injection site reactions (19 [22.6%] vs. 3 [5.5%], P=0.016) without a significant difference in the incidence of serious infections (11 [13.1%] vs. 7 [12.7%], P=0.435). Treatment with anakinra significantly reduced the area under the curve for high-sensitivity C-reactive protein between baseline and 14 days (75.48 [41.7-147.47] vs. 222.82 [117.22-399.28] mgday/L, P<0.001). IL-1 blockade with anakinra for 14days in patients with STEMI reduces the incidence of new-onset HF or hospitalization for HF at 1year following STEMI.

The safety profile of biologic agents in comparison with non-biologic systemic agents, and topical compounds in the management of psoriasis-A 30-month prospective, observational cohort study.

Although biologic agents (BAs) are very effective, solid data proving they are safer than other therapies in psoriasis are still lacking. A total of 289 psoriatic patients were followed for 30months; of which number 118 were treated with topical agents alone, 112 received BAs, and the remaining 59 patients were on non-biologic systemic agents (NBSAs). The rates of adverse events in these groups were recorded and statistically analysed. Patients treated with BAs had higher rates of adverse events (P=.017), including overall infections (P=.003), respiratory infections (P<.001), renal, urinary (P<.001), musculoskeletal, connective tissue (P<.001, and P=.021) and oral cavity-related (P=.046) disorders. Except for the incidence of infections, all the above adverse events occurred more often in our study than in clinical trials. The occurrence of serious adverse events was P=.066, with the incidence of serious infections being P=.164. Unlike patients on topical therapy and NBSAs, patients treated with BAs were forced to discontinue their therapies (P=.001). The Psoriasis Area Severity Index (PASI) and body surface area (BSA) scores were the lowest among patients on BAs. While BAs were the most effective therapies, they were associated with higher rates of treatment discontinuation and adverse events in comparison with other forms of therapy.

Tofacitinib as a novel therapy in COVID-19 acute respiratory distress syndrome.

Tofacitinib as a novel therapy in COVID-19 acute respiratory distress syndrome.

OP24 Efficacy and safety of upadacitinib induction therapy in patients with Moderately to Severely Active Ulcerative Colitis: Results from the phase 3 U-ACHIEVE study

BackgroundAn unmet therapeutic need remains in patients with ulcerative colitis (UC). U-ACHIEVE is one of two phase 3 induction trials evaluating the safety and efficacy of the selective Janus kinase–1 inhibitor upadacitinib (UPA) 45 mg once daily (QD) in adults with UC.MethodsU-ACHIEVE is a multicentre, double-blind, placebo (PBO)–controlled trial (NCT02819635) that randomized patients with moderately to severely active UC 2:1 to UPA 45 mg QD or PBO for 8 weeks. Patients were stratified by response to biologic therapy (inadequate vs non–inadequate responder), baseline corticosteroid use (yes or no), and baseline adapted Mayo score (≤7 or >7). The primary endpoint was proportion of patients achieving clinical remission (per adapted Mayo Score) at week 8.Ranked secondary endpoints included endoscopic improvement, endoscopic remission, and clinical response per adapted Mayo Score at week 8; clinical response per partial adapted Mayo Score at week 2; and histologic-endoscopic mucosal improvement at week 8. Non-responder imputation incorporating multiple imputations for missing data due to COVID-19 are reported. Safety was assessed through week 8.Results474 patients were randomized (UPA, n=319; PBO, n=155). Baseline characteristics were well balanced between groups (Table 1). A significantly higher proportion of patients receiving UPA (26.1%) vs PBO (4.8%) achieved clinical remission at week 8 (adjusted treatment difference [95% CI], 21.6% [15.8, 27.4]; P<0.001; Figure 1). For all ranked secondary endpoints, UPA was superior to PBO (P<0.001; Figure 1). A significant difference in clinical response favouring UPA vs PBO was seen as early as week 2 (60.1% vs 27.3%) and was sustained over 8 weeks (79.0% vs 41.6%; Figure 2). There were more serious adverse events (AEs), severe AEs, and AEs leading to study drug discontinuation with PBO (Table 2). The most common AEs were acne, creatine phosphokinase elevation, and nasopharyngitis with UPA and worsening of UC and anaemia with PBO. Incidence of serious infection was similar between UPA and PBO. Neutropenia and lymphopenia were reported more frequently with UPA vs PBO (Table 2).No adjudicated gastrointestinal perforation, major cardiovascular AEs, or thrombotic events and no active tuberculosis, malignancy, or deaths were reported. ConclusionIn patients with moderately to severely active UC, UPA 45 mg QD induction therapy was superior to PBO in inducing clinical remission/response, and endoscopic remission/response over 8 weeks; responses were significant and rapid. UPA 45 mg QD was well tolerated; safety was comparable with the known safety profile of UPA, and no new safety signals were identified.

P482 Safety and efficacy of ustekinumab for Crohn’s disease in the elderly population

BackgroundThe rising incidence of inflammatory bowel disease (IBD) worldwide and an ageing population has led to a marked increase in elderly IBD patients. Anti-tumour necrosis factor (TNF) agents are associated with an increased risk of serious infections and treatment discontinuation among elderly IBD patients but little is known about non anti-TNF biologics in this cohort. We aimed to examine safety and efficacy of ustekinumab in elderly Crohn’s disease (CD) patients.MethodsPatients ≥60 years old commencing ustekinumab for CD were included in this retrospective multi-centre cohort study. We gathered data on adverse events, Harvey Bradshaw Index (HBI) and concomitant steroid therapy. The primary outcome was serious infections, defined as requiring hospitalisation. Efficacy was assessed by serial HBI measurement and treatment persistence.Results70 patients were included, with a median age of 68 years (range 60–87), a male:female ratio of 9:5 and a median Charlson co-morbidity index of 4 (range 2–9). 44 (62.9%) had prior anti-TNF exposure and 15 (21.4%) previous vedolizumab. Median treatment duration was 12 months (range 2–48), with a total of 84 patient years. 31 patients (41.3%) had steroids at initiation, and 33 (47.1%) required a course of steroids at a later date.Seven patients (10%) had a combined 9 serious infections, of which 1 was life threatening requiring organ support. Incidence of serious infections was 0.107 per patient year. A further 18 patients had a combined 22 non-severe infections (Table 1). The overall infection rate was 0.417 per patient year. Charlson co-morbidity index was numerically higher among those who developed severe infections (median 5, range 3–7 vs. median 4, range 2–9, P=NS). 3 patients developed a malignancy; non-Hodgkin’s lymphoma, melanoma and prostate cancer.Mean HBI improved from 8.13 at baseline to 4.64 at 6 months and 4.10 at last follow up (both P<0.0001). Treatment persistence rate was 61.4% (N=43) and 36 (51.4%) were steroid-free. Reasons for discontinuation were primary non-response (42%), adverse event (32%), secondary loss of response (10%), malignancy (10%) and lack of funding (5%).Table 1AetiologyNumber of patients (%)SeverePneumonia3 (4.3)Line infection2 (2.9)Covid-191 (1.4)Biliary sepsis1 (1.4)Epididymo-orchitis1 (1.4)Shingles1 (1.4)Non-severeLower respiratory tract9 (12.9)Urinary6 (8.6)Coryzal4 (5.7)Pneumonia1 (1.4)Diarrhoea1 (1.4)Line infection1 (1.4)Soft tissue1 (1.4)ConclusionUstekinumab was safe and effective in a cohort of elderly CD patients. Infections were mostly mild, not resulting in therapy discontinuation. The risk of serious infection was low at 0.107 per patient year of treatment.

Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study

BackgroundThere is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer.MethodsWe conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States.The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted.ResultsThere were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1–8.4).ConclusionsThis real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).

1095. Investigation of Risk Factors Associated with Serious Bacterial, Viral and Invasive Fungal Infections in Hematologic Patients on Ibrutinib

BackgroundIbrutinib is a tyrosine kinase inhibitor used to treat hematologic malignancies that may increase the risk of serious infection including invasive fungal infections (IFI). In a study of 378 patients with hematologic malignancy on ibrutinib, serious infection and IFI occurred in 11% and 4% respectively (Varughese et al. Clin Infect Dis). The primary aims of our study were to determine the incidence of serious infection and associated risk factors in patients on ibrutinib.MethodsWe performed a retrospective analysis of patients with hematologic malignancy prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital from 2014 to 2019 to identify serious infections defined as those requiring inpatient management. We collected demographic, clinical and oncologic data. Chi-squared tests were used to determine factors associated with an increased risk of infection.ResultsA total of 254 patients received ibrutinib including 156 with CLL, 89 with NHL and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. There were 51 (20%) patients with serious infections including 45 (17.7%) bacterial, 9 (3.5%) viral and 5 (2%) IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis). Anti-mold prophylaxis was prescribed to 7 (2.8%) patients, none of whom developed IFI. Risk factors associated with serious infection included ECOG score ≥ 2 (OR 4.6, p < 0.001), concurrent steroid use (≥ 10 mg prednisone daily for ≥ 2 weeks; OR 3.0, p < 0.001), neutropenia (OR 3.6, p < 0.01), lymphopenia (OR 2.4, p < 0.05) and maximum ibrutinib dose of 560 mg (OR 2, p < 0.05). There was a dose dependent increase in infections based on number of chemotherapy regimens prior to ibrutinib initiation: 14.3% with 0, 19.7% with 1-2 and 28.7% with ≥ 3 prior treatments.ConclusionThe incidence of serious infection in hematologic patients on ibrutinib was higher than previously reported (20% versus 11%) but the rate of IFI was lower (2% versus 4%). High ECOG score, leukopenia, steroids, and higher ibrutinib doses were associated with an increased risk for serious infection. Targeted antimicrobial prophylaxis should be considered for patients on ibrutinib with these risk factors. Improving functional status may also reduce the risk of infection in patients on ibrutinib.Disclosures All Authors: No reported disclosures

1092. Increased Risk of Serious Infections in Mantle Cell Lymphoma Versus Other Hematologic Malignancies in Patients on Ibrutinib

BackgroundIbrutinib, a tyrosine kinase inhibitor used for treatment of hematologic malignancies, is associated with an increased risk of infection including invasive fungal infections (IFI). However, the risk of infection may vary across different types of malignancies. The primary aims of our study were to determine the incidence of serious infection and associated risk factors in different hematologic malignancies while on ibrutinib.MethodsWe performed a retrospective analysis of patients prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital between January 2014 and July 2019 by chart review. We collected demographic, and clinical data along with oncologic history, and identified serious infections defined as those requiring inpatient management. Chi-squared tests were used to determine characteristics associated with an increased risk of infection.ResultsA total of 254 patients on ibrutinib were identified including 156 with CLL, 89 with NHL including 20 with Mantle Cell Lymphoma (MCL) and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. Of 51 patients with serious infections, 10 (20%) had MCL, 11 (20.3%) had other NHLs, 28 (54.9%) had CLL and 2 (3.9%) had other malignancies. The relative frequency of serious infections was higher in MCL than non-MCL (50% vs. 17.1%). More MCL patients experienced IFI (1 pulmonary cryptococcosis, 2 pulmonary aspergillosis), compared to non-MCL patients (2 pulmonary aspergillosis; 15% vs. 0.9%). Risk factors associated with serious infection in MCL included maximum ibrutinib dose of 560 mg (OR 16.4, p < 0.001), other concurrent chemotherapy (OR 8.2, p < 0.001), prior HSCT (OR 5.9, p < 0.001), concurrent steroid use (≥ 10 mg prednisone for ≥ 2 weeks; OR 2.4, p < 0.05), lymphopenia (OR 2.4, p < 0.05) a history of prior chemotherapy (OR 0.2, p < 0.05) and ECOG score ≥ 2 (OR 3.2, p < 0.01).ConclusionIn this study of hematologic malignancy on ibrutinib, MCL patients had a greater risk of serious infection. This increased risk in MCL could be associated with more prolonged and intense immunosuppression rather than underlying disease pathogenesis. Antimicrobial prophylaxis should be considered in MCL patients on ibrutinib to mitigate risk of infection.Disclosures All Authors: No reported disclosures

Immunomodulatory drugs increase the risk of serious infections in multiple myeloma patients: A meta-analysis using real-world data

Background: Immunomodulatory drugs like thalidomide, pomalidomide, and others are commonly used for the management of multiple myeloma. Epidemiological evidence showed variable findings. So, this meta-analysis is aimed to understand the association of immunomodulatory drug use and the risk of infections. Methods and materials: This meta-analysis was performed by adhering to the preferred reporting items for systematic review and meta-analysis guidelines. PubMed and Embase electronic databases were searched by two independent investigators. The study search period was from inception to September 2019. Only those observational studies qualified for inclusion which reported the association between any of the immunomodulatory drug's use and risk of serious infections. Study quality of included studies was assessed using the Newcastle-Ottawa scale. The primary outcome of this study was to investigate the rate of infections in multiple myeloma patients treated with immunomodulatory drugs. Secondary outcomes include risk based on different types of immunomodulatory drugs. All the analysis was done with RevMan software. Results: This meta-analysis was based on 3224 patients from all the included studies with a mean age range from 54 y to 75 y. Included studies reported infection incidence from 1.54% to 21.88%. Due to the significant heterogeneity, the random effect model was applied. Pooled incidence of infection due to immunomodulatory agents was 8.80% (95% CI: 6.90%–10.70%). The pooled incidence of serious infection among pomalidomide users with relapsed and refractory cases was 11.80% (95% CI: 6.50%–17.10%). Thalidomide user has a higher incidence in multiple myeloma patients who were on induction therapy 8.70% (95% CI: 5.40%–11.90%). Whereas the pooled incidence was lower in thalidomide user who was on maintenance therapy2.70% (95% CI: 0–6.70%). Conclusion: A higher risk of infections was observed in multiple myeloma patients receiving immunomodulatory therapy. Preventive management is essential for patients.

Hypogammaglobulinemia after rituximab for rheumatoid arthritis is not rare and is related with good response: 13 years real-life experience.

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. 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. 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. 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.

Initial mycophenolate dose in tacrolimus treated renal transplant recipients, a cohort study comparing leukopaenia, rejection and long-term graft function

The evidence supporting an initial mycophenolate mofetil (MMF) dose of 2 g daily in tacrolimus-treated renal transplant recipients is limited. In a non-contemporaneous single-centre cohort study we compared the incidence of leukopaenia, rejection and graft dysfunction in patients initiated on MMF 1.5 g and 2 g daily. Baseline characteristics and tacrolimus trough levels were similar by MMF group. MMF doses became equivalent between groups by 12-months post-transplant, driven by dose reductions in the 2 g group. Leukopaenia occurred in 42.4% of patients by 12-months post-transplant. MMF 2 g was associated with a 1.80-fold increased risk of leukopaenia compared to 1.5 g. Rejection occurred in 44.8% of patients by 12-months post-transplantation. MMF 2 g was associated with half the risk of rejection relative to MMF 1.5 g. Over the first 7-years post-transplantation there was no difference in renal function between groups. Additionally, the development of leukopaenia or rejection did not result in reduced renal function at 7-years post-transplant. Leukopaenia was not associated with an increased incidence of serious infections or rejection. This study demonstrates the initial MMF dose has implications for the incidence of leukopaenia and rejection. Since neither dose produced superior long-term graft function, clinical equipoise remains regarding the optimal initial mycophenolate dose in tacrolimus-treated renal transplant recipients.

Changes in selected haematological parameters associated with JAK1/JAK2 inhibition observed in patients with rheumatoid arthritis treated with baricitinib

ObjectiveTo characterise changes in selected haematological parameters following once-daily oral baricitinib dosing.MethodsData were pooled from eight randomised clinical trials (four phase 3, three phase 2, one phase 1b) and one...

Performance of the RABBIT infection risk score in an Argentinian rheumatoid arthritis cohort.

Patients with rheumatic autoimmune diseases have a higher risk of infections compared with age-and sex-matched controls. In Latin America, there are no validated tools to assess the risk of serious infection. The objectives were to estimate the incidence of serious infections in a cohort of rheumatoid arthritis (RA) patients followed for 12 months and to validate the RABBIT risk score for serious infections. Patients with RA were included and followed for 12 months. Baseline sociodemographic data, comorbidities, RA characteristics, and vaccination status were recorded. The baseline RABBIT risk score was calculated. Serious infections were documented, describing site and time since enrollment. Six hundred five patients were included (13 centers). The incidence of serious infection was 5% (95% CI 3-7). The most frequent sites were respiratory and urinary (90%). Performance of RABBIT risk score: patients with no infection during follow-up had a median score of 1.2 (IQR 0.8-2.1) and patients with infection 5.1 (IQR 2.15-12.6) p 0.00001. ROC curve analysis: AUC 0.86 (95% CI 0.8-0.94), best cut-off 2.85 (sensibility 75%, specificity 85%). The incidence of serious infections was 5% during the follow-up. The RABBIT score performed excellently in our patients. Key Points • The RABBIT risk score for serious infections showed an excellent performance in a population different (Latin America) from the original one included in the German registry. • This may assist rheumatologists in selecting drugs for patients according to the individual risk of infection, in a fast and simple way.

Multicentre retrospective cohort study assessing the incidence of serious infections in patients with lupus nephritis, compared with non-renal systemic lupus erythematosus

ObjectivesThe incidence of serious infections is poorly defined in patients with lupus nephritis (LN). It is also unclear if LN influences risk of serious infections in a longitudinal analysis. The...

ICHIBAN, a non-interventional study evaluating tocilizumab long-term effectiveness and safety in patients with active rheumatoid arthritis

We aimed to measure long-term effectiveness and safety of tocilizumab in patients with rheumatoid arthritis in daily German practice. ICHIBAN was a prospective, multi-centre, non-interventional study (ML22928) that enrolled adult patients with active moderate to severe rheumatoid arthritis. Patients were to be treated according to tocilizumab label and observed for up to two years. Effectiveness outcomes included DAS28-ESR remission, EULAR response, CDAI and HAQ. Overall, 3164 patients received at least one dose of tocilizumab. Patient mean age was 55.5±13.1 years (74.8% female). At baseline, 72.1% of patients had at least one comorbidity. Approximately 50.9% of patients received concomitant csDMARDs, mostly methotrexate, and 80.7% received concomitant glucocorticoids (GCs). In patients receiving GCs at baseline, the mean dose decreased from 9.32±16.36 mg/d to 4.60±4.48 mg/d at week 104. In the effectiveness population with no prior TCZ (n=2902), 61.4% of patients achieved the primary outcome, DAS28-ESR remission. Improvements were seen as early as week 4. At week 104, 77.9% of patients had DAS28-ESR low disease activity, 89.6% achieved good or moderate EULAR response, and 29.5% achieved a CDAI-based remission. Effectiveness outcomes were similar in all previous therapy subgroups. The incidence of serious infections was similar to the rates in former studies involving tocilizumab. Patients receiving GC at baseline experienced slightly higher rates of treatment-related serious adverse events, mainly infections. No new safety signals were observed. Long-term effectiveness and safety in ICHIBAN were in line with previously reported tocilizumab efficacy and safety studies.

GM-CSF in the treatment of COVID-19: a new conductor in the pathogenesis of cytokine storm?

GM-CSF in the treatment of COVID-19: a new conductor in the pathogenesis of cytokine storm?

Efficacy and safety of sarilumab in combination with csDMARDs or as monotherapy in subpopulations of patients with moderately to severely active rheumatoid arthritis in three phase III randomized, controlled studies

BackgroundThe interleukin-6 receptor inhibitor sarilumab demonstrated efficacy in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy in patients with moderately to severely active rheumatoid arthritis (RA) with an inadequate response (IR) or intolerant (INT) to methotrexate (MTX) or tumour necrosis factor (TNF)-α inhibitors. This analysis investigated the efficacy and safety of sarilumab in patient subgroups.MethodsData were included from phase III studies: two placebo-controlled studies of subcutaneous sarilumab 150/200 mg every 2 weeks (q2w) either + MTX in MTX-IR patients (52 weeks) or + csDMARDs in TNF-IR/INT patients (24 weeks), and a monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w in MTX-IR/INT patients (24 weeks). Prespecified and post hoc subgroups included patient demographics, disease characteristics, and prior treatments. Prespecified and post hoc endpoints included clinical, radiographic, and physical function measures, and p values are considered nominal. Safety was assessed during double-blind treatment.ResultsThe superiority of sarilumab (either as monotherapy vs. adalimumab or in combination with csDMARDs vs. placebo + csDMARDs) across clinical endpoints was generally consistent across subgroups defined by patient demographics, disease characteristics, and prior treatments, demonstrating the benefit of sarilumab treatment for a wide range of patient types. Interaction p values of < 0.05 were consistently observed across studies only for baseline anti-cyclic citrullinated peptide antibody (ACPA) status for American College of Rheumatology 20% response, but not American College of Rheumatology 50% or 70% response. Adverse events and worsening laboratory parameters occurred more frequently in sarilumab-treated vs. placebo-treated patients and were more frequent in the small number of patients ≥ 65 years (n = 289) vs. patients < 65 years (n = 1819). Serious infections occurred in six patients aged ≥ 65 years receiving sarilumab, although the incidence of serious infections was generally higher in patients aged ≥ 65 years regardless of treatment.ConclusionsApart from ACPA status, there were no consistent signals indicating differential effects of sarilumab in any of the subpopulations assessed. Sarilumab demonstrated consistent efficacy and safety across a wide range of patients with RA.Trial registrationClinicalTrials.gov NCT01061736, registered on February 03, 2010; ClinicalTrials.gov NCT01709578, registered on October 18, 2012; ClinicalTrials.gov NCT02332590, registered on January 07, 2015

COVID-19: the new challenge for rheumatologists

Currently, the infection caused by the new coronavirus COVID-19 is considered by the global community as an emergency of international concern. Rheumatologists are particularly concerned about this problem, since patients with immune-mediated inflammatory rheumatic diseases (IMIRDs) are at higher risk for infectious diseases and receive immunosuppressive treatment. The use of disease-modifying antirheumatic drugs and biological agents increases the incidence of serious infections, but insufficient/no monitoring of IMIRD activity is an even greater risk factor for infectious complications. In addition, the role of vaccination mainly against influenza and pneumococcal infection is substantially increasing in modern conditions, since the risk of death from respiratory tract infections is quite high in patients with IMIRDs, which is very important in the context of the current COVID-19 pandemic.The paper presents an update on the incidence of viral infections in patients with IMIRDs and also discusses whether antirheumatic drugs can be used to treat COVID-19.

Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER).

ObjectiveTo assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. MethodsAll patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria and disease onset <18 years old (jSLE), were retrospectively investigated for SI (defined as either the need for hospitalization with antibacterial therapy for a potentially fatal infection or death caused by the infection). Standardized SI rate was calculated per 100 patient years. Patients with and without SI were compared. Bivariate and multivariate logistic and Cox regression models were built to calculate associated factors to SI and relative risks. ResultsA total of 353 jSLE patients were included: 88.7% female, 14.3 years (± 2.9) of age at diagnosis, 16.0 years (± 9.3) of disease duration and 31.5 years (±10.5) at end of follow-up. A total of 104 (29.5%) patients suffered 205 SI (1, 55.8%; 2-5, 38.4%; and ≥6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2–4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. ConclusionsThe risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy.

Malignancy and infection risk during adalimumab therapy in hidradenitis suppurativa.

The association of adalimumab therapy with malignancy and infection is established in other inflammatory diseases; however, rates of hidradenitis suppurativa (HS) are based on case reports or retrospective healthcare data and the effect of adalimumab therapy on these rates is unknown. Previously reported rates in the PIONEER OLE Phase 3 study reported on rates only in a subpopulation of 88 participants rather than the entire cohort. To quantify rates of malignancy and serious infection in all patients with HS treated with adalimumab 40mg weekly. Reanalysis was undertaken of individual patient data from the PIONEER 1, PIONEER 2 and PIONEER open-label extension Phase 3 trial data encompassing 591 unique patients with HS administered adalimumab 40mg weekly without concurrent antibiotic exposure. Incidence rates of serious infection and malignancy were calculated. Incidence rates of serious infection and malignancy were 2.14 and 0.46 per 100 patient-years, respectively. Rates of infection and malignancy were comparable to those in other inflammatory conditions examined. Incidence of serious infection in patients with HS on adalimumab is comparable to those with psoriasis and inflammatory arthropathies, but the incidence of malignancy is increased. This may reflect disease-specific malignancy risk rather than an effect of adalimumab.