Cancer risk with tocilizumab/sarilumab, abatacept, and rituximab treatment in patients with rheumatoid arthritis: a Danish cohort study.

OBJECTIVES: To investigate cancer risk in rheumatoid arthritis (RA) patients treated with tocilizumab/sarilumab, abatacept, or rituximab compared with those who received tumour necrosis factor inhibitors (TNFi) and compared with biological disease-modifying anti-rheumatic drugs (bDMARD) naïve RA patients. METHODS: Nationwide registry-based cohort study of RA patients initiating treatment with tocilizumab/sarilumab, abatacept, rituximab, TNFi, and bDMARD-naive patients their second type of conventional synthetic DMARD (csDMARD). Patients were identified in DANBIO and followed for cancer from 2006-2020. Patients could contribute multiple treatments, with person years (PYRS), deaths, and cancers allocated to each treatment group in a 'latest type of treatment' manner. Inverse probability of treatment weighting and weighted cause-specific Cox models were used to calculate hazard ratios (HRs) for cancer in each tocilizumab/sarilumab, abatacept, and rituximab group compared with TNFI and bDMARD naïve groups, respectively. RESULTS: In total, 21 982 treatment initiations, 96 475 PYRS, and 1423 cancers were identified. There were no statistically significant increased HRs for overall cancer in tocilizumab/sarilumab, abatacept, or rituximab treatment groups (HRs ranged from 0.7-1.1). More than five years of abatacept exposure showed a non-significantly increased HR compared with TNFi (HR 1.41, 95% confidence intervals CI 0.74-2.71). For hematological cancers, rituximab treatment showed non-significantly reduced HRs: vs TNFi (HR 0.09; 95%CI 0.00-2.06) and bDMARD-naïve (HR 0.13; 95%CI 0.00-1.89). CONCLUSION: Treatment with tocilizumab/sarilumab, abatacept, or rituximab in RA patients was not associated with increased risks of cancer compared with TNFi-treated and with bDMARD-naïve RA patients in a real-world setting.

Cancer risk in patients with rheumatoid arthritis treated with janus kinase inhibitors: a nationwide Danish register-based cohort study.

OBJECTIVES: We aimed to investigate the risk of first primary cancer in patients with RA treated with janus kinase inhibitors (JAKi) compared with those who received biologic DMARDs (bDMARDs) in a real-world setting. METHODS: We performed an observational cohort study using the nationwide registers in Denmark. Patients with RA aged 18+ years, without a previous cancer diagnosis, and who initiated treatment with JAKi or bDMARDs from 1 January 2017 to 31 December 2020 were followed for any cancer (except non-melanoma skin cancer). We applied inverse probability of treatment weighting (IPTW) to account for covariate differences between treatment groups. IPTW-generated weights were used with cause-specific Cox (CSC) models to calculate hazard ratios (HRs) for cancer incidence in JAKi-treated compared with bDMARD-treated patients with RA. RESULTS: We identified 875 and 4247 RA patients treated with JAKi and bDMARDs, respectively. The JAKi group contributed 1315 person years (PYRS) and 19 cancers, the bDMARD group contributed 8597 PYRS and 111 cancers, with corresponding crude incidence rates per 1000 PYRS of 14.4 and 12.9. Comparing the two groups using weighted CSC models, a HR of 1.41 (95% CI 0.76, 2.37, 95% CIs) was seen for JAKi- vs bDMARD-treated patients with RA. CONCLUSION: JAKi treatment in real-world patients with RA was not associated with a statistically significant increased risk of first primary cancer compared with those who received bDMARDs. However, several numerically increased risk estimates were detected, and a clinically important excess risk of cancer among JAKi recipients cannot be dismissed.

Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study).

BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

COVID-19 infection and hospitalization risk according to vaccination status and DMARD treatment in patients with rheumatoid arthritis.

OBJECTIVES: The objectives of this study were to investigate the incidence of COVID-19 hospitalization in unvaccinated and vaccinated patients with RA compared with matched controls, and in patients with RA according to DMARD treatment. METHODS: This was a Danish nationwide matched-cohort study from January to October 2021. Patients with RA were identified in the DANBIO register and matched 1:20 with individuals from the general population on age, sex, and vaccination status. Primary and secondary outcomes were COVID-19 hospitalization (Danish National Patient Register) and first-time positive SARS-CoV-2 PCR test (Danish COVID-19 Surveillance Register), respectively. Stratified by vaccination status, incidence rates (IRs) per 1000 person years (PYs) and comorbidity-adjusted hazard ratios (aHRs) in cause-specific Cox models were calculated with 95% confidence intervals. RESULTS: In total, 28 447 unvaccinated patients and 568 940 comparators had IRs for COVID-19 hospitalization of 10.4 (8.0-13.4) and 4.7 (4.3-5.1) per 1000 PYs, respectively (aHR 1.88, 1.44-2.46). When fully vaccinated, corresponding IRs were 0.9 (0.5-1.6) and 0.5 (0.4-0.6) per 1000 PYs (aHR 1.94, 1.03-3.66). Unvaccinated RA patients had an aHR of 1.22 (1.09-1.57) for testing positive for SARS-CoV-2 and 1.09 (0.92-1.14) among vaccinated RA patients. Vaccinated rituximab-treated patients had increased crude IR of COVID-19 hospitalization compared with conventional DMARD-treated patients. CONCLUSION: The incidence of COVID-19 hospitalization was increased for both unvaccinated and vaccinated patients with RA compared with controls. Importantly, the parallel decreasing risk for patients with RA suggests a comparable relative benefit of vaccination in most patients.

Incidence of COVID-19 Hospitalisation in Patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study from Denmark.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) have an increased risk of infections due to impaired immune functions, disease activity, and treatment. This study investigated the impact of having SLE on the incidence of hospitalisation with COVID-19 infection. METHODS: This was a nationwide cohort study from Denmark between 1 March 2020 to 2 February 2021, based on the linkage of several nationwide registers. The adjusted incidence of COVID-19 hospitalisation was estimated for patients with SLE compared with the general population in Cox-regression models. Among SLE patients, the hazard ratio (HR) for hospitalisation was analysed as nested case-control study. RESULTS: Sixteen of the 2533 SLE patients were hospitalised with COVID-19 infection. The age-sex adjusted rate per 1000 person years was 6.16 (95% CI 3.76-10.08) in SLE patients, and the corresponding hazard ratio was 2.54 (95% CI 1.55-4.16) compared with the matched general population group after adjustment for comorbidities. Among SLE patients, hydroxychloroquine treatment was associated with a HR for hospitalisation of 0.61 (95% CI 0.19-1.88), and 1.06 (95% CI 0.3-3.72) for glucocorticoid treatment. CONCLUSION: Patients with SLE were at increased risk of hospitalisation with COVID-19.

Increased cancer risk in patients with cutaneous lupus erythematosus and systemic lupus erythematosus compared with the general population: A Danish nationwide cohort study.

OBJECTIVES: To investigate if patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) have an increased risk of cancer compared with the general population, and furthermore to identify specific cancer types associated with increased risk. METHODS: This is an observational cohort study of 5310 patients with CLE or SLE identified in the Danish National Patient Register from 1 January 1995 to 31 December 2014. The cohort was followed up for cancer by linkage to the Danish Cancer Registry. Based on the age, sex, and calendar specific cancer rates of the general population of Denmark, standardised incidence ratios (SIRs) were calculated. RESULTS: The patients with CLE or SLE were followed for 40.724 person-years, each group's average duration of follow-up being 6.9 and 8.1 years. The SIR for overall cancer (except non-melanoma skin cancer (NMSC)) was increased in patients with CLE 1.35 (95%CI 1.15 to 1.58) and patients with SLE 1.45 (95%CI 1.30 to 1.62). Both groups had high risks of hematological - including a 3-4-fold increased risk of non-Hodgkin lymphoma -, pancreatic, and lung cancers. Several cancers associated with oncogenic viruses as liver and tongue/mouth/pharynx were increased in the SLE group, while the risk of ovarian cancer was increased 2-4-fold only in the CLE group. CONCLUSION: The overall risk of cancer was significantly increased in both patients with CLE and SLE. SIRs for hematological, pancreatic and lung cancers were elevated in both groups. Extra awareness of cancer in patients with SLE and patients with CLE should be considered.

Incidence and severeness of COVID-19 hospitalization in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark.

OBJECTIVES: To estimate the incidence of COVID-19 hospitalization in patients with inflammatory rheumatic disease (IRD); in patients with RA treated with specific DMARDs; and the incidence of severe COVID-19 infection among hospitalized patients with RA. METHODS: A nationwide cohort study from Denmark between 1 March and 12 August 2020. The adjusted incidence of COVID-19 hospitalization was estimated for patients with RA; spondyloarthritis including psoriatic arthritis; connective tissue disease; vasculitides; and non-IRD individuals. Further, the incidence of COVID-19 hospitalization was estimated for patients with RA treated and non-treated with TNF-inhibitors, HCQ or glucocorticoids, respectively. Lastly, the incidence of severe COVID-19 infection (intensive care, acute respiratory distress syndrome or death) among hospital-admitted patients was estimated for RA and non-IRD sp - individudals. RESULTS: Patients with IRD (n = 58 052) had an increased partially adjusted incidence of hospitalization with COVID-19 compared with the 4.5 million people in the general population [hazard ratio (HR) 1.46, 95% CI: 1.15, 1.86] with strongest associations for patients with RA (n = 29 440, HR 1.72, 95% CI: 1.29, 2.30) and vasculitides (n = 4072, HR 1.82, 95% CI: 0.91, 3.64). There was no increased incidence of COVID-19 hospitalization associated with TNF-inhibitor, HCQ nor glucocorticoid use. COVID-19 admitted patients with RA had a HR of 1.43 (95% CI: 0.80, 2.53) for a severe outcome. CONCLUSION: Patients with IRD were more likely to be admitted with COVID-19 than the general population, and COVID-19 admitted patients with RA could be at higher risk of a severe outcome. Treatment with specific DMARDs did not affect the risk of hospitalization.