Efficacy Of Baricitinib in Patients With Moderate-To-Severe Rheumatoid Arthritis Up to 6.5 Years Of Treatment: Results Of A Long-Term Study.

OBJECTIVES: To evaluate the long-term efficacy of once-daily baricitinib 4 mg or 2 mg in patients with active rheumatoid arthritis who had inadequate response (IR) to MTX, csDMARDs, or bDMARDs. METHODS: Data from three completed phase III studies, RA-BEAM (MTX-IR), RA-BUILD (csDMARD-IR), and RA-BEACON (bDMARD-IR), and one completed long-term extension study (RA-BEYOND) were analyzed up to 6.5 years (340 weeks [RA-BEAM] and 336 weeks [RA-BUILD and RA-BEACON]). Low disease activity (LDA) (Simplified Disease Activity Index [SDAI] ≤11), clinical remission (SDAI ≤3.3), and physical function (Health Assessment Questionnaire Disability Index [HAQ-DI] ≤0.5) were the main outcomes assessed. Completer and non-responder imputation (NRI) analyses were conducted on each population. RESULTS: At week 340 or 336, LDA was achieved in 37%/83% of MTX-IR, 35%/83% of csDMARD-IR, and 23%/73% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. Remission was achieved in 20%/40% of MTX-IR, 13%/32% of csDMARD-IR, and 9%/30% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. HAQ-DI ≤0.5 was reached in 31%/51% of MTX-IR, 25%/46% of csDMARD-IR, and 24%/38% of bDMARD-IR patients treated with baricitinib 4 mg, assessed by NRI/completer analyses, respectively. CONCLUSION: Treatment with baricitinib 4 mg or 2 mg demonstrated efficacy up to 6.5 years with maintained LDA/remission results across SDAI, CDAI and DAS28-hsCRP consistent with previously reported data, and was well tolerated.

Real-world utilisation and switching between Janus kinase inhibitors in Australian patients with rheumatoid arthritis in the OPAL dataset.

OBJECTIVES: To describe use and treatment persistence for Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) by line of therapy, and the mechanism of action for the drug switched to after JAKi discontinuation. METHODS: This was a retrospective, observational analysis using the OPAL dataset, a large collection of deidentified electronic medical records from 112 rheumatologists around Australia. Adult patients with RA were included if they initiated tofacitinib (TOF), baricitinib (BARI) or upadacitinib (UPA) between 1 October 2015 and 30 September 2021. Data were summarised using descriptive statistics. Kaplan-Meier survival was used to analyse treatment persistence. RESULTS: 5,900 patients initiated JAKi within the study window (TOF n=3,662, BARI n=1,875, UPA n=1,814). Median persistence was similar across JAKi within each line of therapy where there was sufficient follow-up, and almost 3 years for first-line: 34.9 months (95% CI 30.8, 40.7; n=1,408) for TOF, 33.6 months (95% CI 25.7, not reached; n=545) for BARI. While JAKi to JAKi switching occurred across all lines of therapy, switches to a tumour necrosis factor inhibitor (TNFi) were more frequent after first- or second-line JAKi. JAKi monotherapy use at baseline increased with line of therapy, and was highest at follow-up after switching to another JAKi. 'Lack of efficacy' was the most common reason for discontinuing JAKi. CONCLUSIONS: In this large analysis of Australian real-world practice separated by line of therapy, treatment persistence for JAKi was high overall subject to differential follow-up, but declined in later lines. JAKi to JAKi switching was observed across all lines of therapy.

Are SMAD2/4/7 genetic variants associated with rheumatoid arthritis susceptibility and severity?

OBJECTIVES: SMADs play one of the key roles in the TGFß signalling pathway. Therefore, through their involvement in the immune response as well as in the fibrosis process, these proteins appear to take on one of the essential functions in the pathogenesis of autoimmune connective tissue diseases such as RA. This study aimed to investigate the association of selected SNPs in SMAD2/4/7 with RA risk in the Caucasian population and disease course in RA patients. METHODS: The study was conducted on 647 patients with established RA and 496 unrelated healthy controls (HCs). All patients fulfilled the American College of Rheumatology Diagnostic classification criteria for RA (ACR 1987). The analysis has been conducted using TaqMan genotyping assay. Transcript-inferred pathogenicity score (TraP-score) has been evaluated by TrapScore. PredictSNP.2 has been used to predict the effect of amino acid substitutions. RESULTS: The present study revealed in SMAD4 a significantly higher frequency of AG rs12456284 (under codominant model OR=0.62 p=0.027 and overdominant model OR=0.59 p=0.016) and GA rs10502913 (under codominant model OR=0.65 p=0.050 and overdominant OR=0.64 p=0.033) genotypes in healthy subjects in comparison to RA patients. Additionally, very strong LD has been noted between these two genetic variants (D'=0.95 r2=0.90). Moreover, bioinformatic analysis classified rs12456284 as deleterious change with 94% prediction accuracy. SMAD2 rs1792666 and SMAD7 rs3736242 showed to have the highest association with disease course. SMAD4 rs10502913, SMAD7 rs3736242, and SMAD7 rs4464148 were associated with the concentration of creatinine. CONCLUSIONS: Our results suggested that rs12456284 and rs10502913 in SMAD4 may have a potential protective effect against RA. Particularly, SMAD2 rs1792666 and SMAD7 rs3736242 seem to be significantly associated with diseases course in RA patients in the Caucasian population.

Relative Impact of Pain and Disease Activity on Improvements in Fatigue: Results From 2 Baricitinib Phase 3 Clinical Trials.

BACKGROUND/OBJECTIVE: Fatigue is common in patients with rheumatoid arthritis (RA). We assessed the relative impact of pain and disease activity on improvements in fatigue in 2 phase 3 baricitinib clinical trials. METHODS: RA-BEAM (NCT01710358) and RA-BEACON (NCT01721044) were randomized, double-blind, placebo-controlled studies in adults with moderate to severe RA. RA-BEAM assessed baricitinib + methotrexate (MTX) and adalimumab + MTX in patients with prior inadequate response/intolerance (IR) to MTX (MTX-IR). RA-BEACON assessed patients with IR to ≥1 biologic disease-modifying antirheumatic drug (bDMARD-IR). Measures included the Functional Assessment of Chronic Illness Therapy-Fatigue scale, Clinical Disease Activity Index (CDAI) for RA, and pain visual analog scale (VAS). Analyses were implemented separately for each study. RESULTS: Significant improvements were seen in disease activity and pain, which were greater with baricitinib versus adalimumab. A statistically significant improvement was seen in fatigue with both active treatments versus placebo. Moderate correlations were observed between improvements in disease activity and fatigue and between improvements in pain and fatigue in both MTX-IR and bDMARD-IR patients. Reductions in pain (≥50%) and remission or low disease activity (CDAI ≤10) had significant associations with fatigue improvement at week 24. In mediation analysis, improvements in fatigue attributable to CDAI and pain VAS in MTX-IR patients were 31% and 52%, respectively, for baricitinib, and 30% and 47%, respectively, for adalimumab. In bDMARD-IR patients, improvement in fatigue was attributed 48% to CDAI and 48% to pain VAS. CONCLUSIONS: In both MTX-IR and bDMARD-IR patients, a large proportion of improvements in fatigue across treatment arms were accounted for by improvements in pain and disease activity.

Baricitinib further enhances disease-modifying effects by uncoupling the link between disease activity and joint structural progression in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate if baricitinib, a Janus kinase inhibitor, further enhances disease-modifying effects by uncoupling the link between disease activity and structural damage progression in patients with rheumatoid arthritis (RA) using two phase III randomised, double-blinded trials. METHODS: In RA-BEAM, patients with established RA and inadequate response to methotrexate (MTX-IR) received placebo (PBO), baricitinib 4 mg or adalimumab 40 mg on background MTX. In RA-BEGIN, conventional synthetic disease-modifying antirheumatic drug (csDMARD)-naïve patients received MTX, baricitinib 4 mg or baricitinib 4 mg plus MTX. Using linear regression analyses, joint damage progression (assessed by change from baseline in van der Heijde modification of the Total Sharp Score) was compared between treatment groups for patients achieving certain disease activity states by the Clinical Disease Activity Index. Time-averaged postbaseline responses were used to week 24 (RA-BEAM) and week 52 (RA-BEGIN). RESULTS: For MTX-IR patients, structural damage progression was reduced regardless of disease activity states in baricitinib-treated patients (p=0.6), whereas in PBO patients there was a clear dependence on disease activity states, being significantly lower in those who achieved remission/low disease activity (REM/LDA) compared with moderate/high disease activity (MDA/HDA) (p=0.02). Furthermore, the baricitinib MDA/HDA group had less damage progression than the PBO MDA/HDA group (p<0.001). For csDMARD-naïve patients, progression was lower in REM/LDA versus MDA/HDA within the MTX group (p<0.001). However, for baricitinib+MTX (p=0.5) or baricitinib monotherapy (p=0.07), progression was similar regardless of disease activity. In MDA/HDA groups, progression was lower with baricitinib+MTX (p<0.001) and numerically lower with baricitinib monotherapy (p=0.07) versus MTX. C reactive protein (≤5 mg/L and >5 mg/L) sensitivity analyses supported the primary findings. CONCLUSIONS: Baricitinib reduces structural damage progression versus PBO with background MTX and/or MTX, even in patients with MDA/HDA, showing a disease-modifying effect across all disease activity states.

IL-1ß, IL-10 and TNF-α polymorphisms may affect systemic lupus erythematosus risk and phenotype.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease, and IL-1ß, IL-10, and TNF-α genes are important in the pathogenesis of this disease. We studied the impact of IL-1ß-511, IL-1ß +3953, IL-10 -592, IL-10 -1082, TNF-α -308, TNF-α -238, and TNF-α +489 polymorphisms on SLE risk and phenotype in SLE patients and healthy controls. METHODS: We genotyped SLE patients and healthy controls by real-time PCR on QuantStudio 5 (Applied Biosystems) and measured levels of cytokines by enzyme-linked immunosorbent assay (ELISA). RESULTS: We indicated that TNF-α -308, IL-10 -592, IL-10 -1082, IL-1ß-511 and IL-1ß +3953 polymorphisms affect SLE risk. Furthermore, we exposed that some of the TNF-α +489, TNF-α -238, IL-10 -1082 and IL-1ß +3953 genotypes are connected with the SLE phenotype. Moreover, we discovered the linking between specific genotypes and the serum concentrations of TNF-α, IL-1ß, and IL-10. CONCLUSIONS: In conclusion, our study revealed that IL-1ß-511, IL-1ß +3953, IL-10 -592, IL-10 -1082, and TNF-α -308 polymorphisms may affect SLE risk and phenotype.

Tissue factor and human apolipoprotein H genetic variants and pro-inflammatory cytokines in systemic lupus erythematosus patients.

OBJECTIVES: Tissue factor (TF) and Human apolipoprotein H (APOH) seem to be significantly associated with a clinical manifestation in systemic lupus erythematosus (SLE) patients with or without APS, mostly because of thrombotic events and coagulation processes. Additionally, according to recent studies, these two factors appear to be an important part of immune response and inflammation. METHODS: The objective of this study was to investigate three SNPs of APOH (rs4581, rs8178835 and rs818819) and three of TF (rs958587, rs3917615, rs1361600) in SLE patients and healthy subjects using TaqMan genotyping assay and their association with inflammatory cytokines level in serum and selected clinical parameters. RESULTS: Present study revealed that TF rs3917615 and rs958587 and APOH rs4581 possibly predispose to joint involvement in SLE. CONCLUSIONS: Analysed genetic variants of TF and APOH may have an impact on inflammatory processes and clinical relevance in SLE patients in the Caucasian population.

IL-35, TNF-α, BAFF, and VEGF serum levels in patients with different rheumatic diseases.

OBJECTIVES: Inflammatory processes in rheumatic diseases spread via various types of immune system cells and tissues with the aid of inflammatory cytokines and growth factors and the participation of vascular endothelium. Research is still conducted to determine the role of individual factors in the pathophysiology of rheumatic diseases. The task is complicated because the multiplane network of cytokines is characterized by complex correlations manifesting as positive and negative feedback, which impedes the definitive interpretation of the role of specific cytokines. Therefore, it seems justified to perform a comparative analysis of the expression of at least several molecules in one study, which may help reveal their role in the pathogenesis of rheumatic diseases and have prognostic value. MATERIAL AND METHODS: The aim of the study involves the assessment and comparative analysis of the concentrations of interleukin 35 (IL-35), tumour necrosis factor α (TNF-α), B-cell-activating factor (BAFF), and vascular endothelial growth factor (VEGF) in peripheral blood serum in patients with rheumatoid arthritis (RA) (n = 43), systemic lupus erythematosus (SLE) (n = 28), antiphospholipid syndrome (APS) (n = 24), and mixed connective tissue disease (MCTD) (n = 9). The main intention is to search for biomarkers for specific rheumatic diseases. Cytokine and growth factor levels were determined using specific ELISA kits. RESULTS: Statistically significant differences in VEGF and IL-35 concentrations occurred between patients with APS vs. RA and SLE vs. RA. There was a significant high positive correlation between the concentration of BAFF and TNF-α (r = 0.77, p < 0.0000) in patients with APS, as well as in patients with SLE (r = 0.55, p = 0.00). CONCLUSIONS: BAFF and TNF-α may be promising biomarkers in patients with APS and VEGF in patients with RA. Additionally, IL-35 may be a useful marker for the diagnosis of APS. Positive correlation of BAFF and TNF-α concentrations in APS and SLE potentially indicates much more similar etiopathogenesis of these diseases than it could be previously predicted.

HIF-1A gene polymorphisms and its protein level in patients with rheumatoid arthritis: a case-control study.

OBJECTIVES: The aim of the study was to identify HIF-1A genetic variants and their possible association with HIF-1α, VEGF, KDR, RORc and Foxp3 protein levels, and susceptibility to and severity of RA. METHODS: The HIF-1A gene polymorphisms were genotyped for 587 RA patients and 341 healthy individuals. The HIF-1α, VEGF, KDR, RORc and Foxp3serum levels were evaluated. RESULTS: Under the codominant model, the frequency of the rs12434438 GG genotype was lower in RA patients than in controls (P = 0.02). Under the recessive model (AA + AG vs GG), the association was also significant (OR 3.32; CI 1.19-9.24; P = 0.02). Overall, rs12434438 A/G and rs1951795 A/C are in almost completed linkage disequilibrium with D' = 0.96 and r2 = 0.85. The HIF-1A rs1951795 A allele was associated with rheumatoid factor (P = 0.02) and mean value of erythrocyte sedimentation rate (ESR) (P = 0.05). In RA patients with HIF-1A rs12434439 GG genotype, the parameters of disease activity such as DAS-28, VAS score, Larsen score or HAQ score were lower compared to RA patients with the HIF-1A rs12434439 AA genotype. Moreover, we also observed that Foxp3 serum levels were higher, and RORc2 serum levels were lower in RA patients with rs12434439 GG. CONCLUSION: The polymorphic HIF-1A rs12434439 GG genotype may play a protective role for RA development.

Antimalarials - are they effective and safe in rheumatic diseases?

Antimalarial drugs (AD) are a group of widespread therapeutic agents in multiple rheumatic indications. Although the effect of AD is mild and extended in time, low toxicity is their appreciated value. This paper describes the current state of knowledge on the mechanism of action, use, toxicity and pleiotropic effects of AD in the pharmacotherapy of autoimmune diseases.

RORC2 Genetic Variants and Serum Levels in Patients with Rheumatoid Arthritis.

BACKGROUND: In the present study, we aimed to evaluate whether polymorphisms within the RORc2 gene are involved in the risk and severity of rheumatoid arthritis (RA). METHODS: 591 RA patients and 341 healthy individuals were examined for RORc2 gene polymorphisms. Serum retinoic acid receptor-related orphan receptor C (RORc) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The rs9826 A/G, rs12045886 T/C and rs9017 G/A RORc2 gene SNPs show no significant differences in the proportion of cases and control. Overall, rs9826 and rs9017 were in high linkage disequilibrium (LD) with D' = 0.952 and r² = 0.874, except rs9826 and rs12045886; and rs12045886 and rs9017 in weak LD. The genotype-phenotype analysis showed a significant association between RORc2 rs9826 A/G and rs9017 G/A single nucleotide polymorphisms (SNPs) and median of C-reactive protein (CRP). Serum RORc levels was higher in RA patients with rs9826AA, rs12045886TT and -TC, and rs9017AA genotypes compared to healthy subjects with the same genotypes (p = 0.02, p = 0.04 and p = 0.01, respectively). Moreover, the median of RORc protein level was higher in RA patients with number of swollen joints bigger then 3 (p = 0.04) and with Health Assessment Questionnaires (HAQ) score bigger then 1.5 (0.049). CONCLUSIONS: Current findings indicated that the RORc2 genetic polymorphism and the RORc2 protein level may be associated with severity of RA in the Polish population.

Do we still need renal biopsy in lupus nephritis?

The natural course of systemic lupus erythematosus (SLE) is characterized by periods of disease activity and remissions. Prolonged disease activity results in cumulative organ damage. Lupus nephritis is one of the most common and devastating manifestations of SLE. In the era of changing therapy to less toxic regimens, some authors have stated that if mycophenolate mofetil can be used for the induction and maintenance treatment in all histological classes of lupus nephritis, renal biopsy can be omitted. This article aims to answer the question of what brings the bigger risk: renal biopsy or its abandonment.

Rivaroxaban - a safe therapeutic option in patients with antiphospholipid syndrome? Our experience in 23 cases.

In the therapeutic approach to patients with antiphospholipid syndrome (APS) with thrombotic manifestations, oral vitamin K antagonists (VKA) remain the standard of care. However, the use of VKA is very often associated with inability to achieve a therapeutic dose even in patients maintaining nutritional and therapeutic restrictions. The non-vitamin-K oral anticoagulants (NOAC) have a lot of advantages, but their efficacy and safety in APS have not been proven. We present 23 patients with APS treated with rivaroxaban in our department. Recurrence of thrombosis was observed only in 1 patient. No major or minor bleeding occurred. It proves the efficacy of treatment with rivaroxaban, but our observations require further prospective, randomized studies.

Immunity and early atherosclerosis in the course of systemic lupus erythematosus, mixed connective tissue disease and antiphospholipid syndrome.

Atherosclerosis is a chronic inflammatory disease of the arteries associated with various risk factors that promote lipid abnormalities, development and progression of atherosclerotic lesions, plaque rupture, and vascular thrombosis. Atherosclerosis is accelerated in autoimmune diseases. Non-invasive investigations showed increased intima-media thickness (IMT), carotid plaque, and coronary artery calcifications in patients with antiphospholipid syndrome, systemic lupus erythematosus and mixed connective tissue disease compared to controls. The balance between the proinflammatory and anti-inflammatory cytokines allows the immune equilibrium to be maintained. In autoimmune diseases the prevalence of proinflammatory factors leads to premature atherosclerosis. This review presents complementary knowledge on innate and adaptive immunity, cytokines and the role of inflammasomes in progression of early atherosclerosis.

Treatment of rheumatic diseases and hepatitis B virus coinfection.

We often encounter rheumatological patients coinfected with hepatitis B in daily practice. In this paper, we will discuss the basic characteristics of the virus of hepatitis B, course of infection, the safety of rituximab, tocilizumab, abatacept treatment and therapeutic recommendations in management of patients with rheumatic diseases.

A JAK Inhibitor for Treatment of Rheumatoid Arthritis: The Baricitinib Experience.

Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, is approved as monotherapy or in combination with methotrexate for treating adults with moderate-to-severe active rheumatoid arthritis (RA) and provides improvements in clinical signs, symptoms and patient-reported outcomes. Currently, baricitinib is approved for treating RA in more than 75 countries. In several pivotal Phase II and III RA trials (RA-BALANCE, RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, RA-BEYOND), up to seven years of baricitinib treatment was well tolerated and provided rapid and sustained efficacy, which was confirmed in real-world settings. Safety signals for another JAK inhibitor, tofacitinib, have emerged, as observed in the post-marketing Phase IIIb/IV trial Oral Rheumatoid Arthritis Trial (ORAL) Surveillance; safety signals were subsequently highlighted in a retrospective study of baricitinib and consequently new recommendations and warnings and precautions for all JAK inhibitors have been issued. Ongoing studies to further characterise and clarify the benefit:risk of JAK inhibitors include registries and controlled trials. This capstone review summarises clinical and real-world data outlining the benefit:risk profile of baricitinib, confirming that the improved disease activity and physical function of patients with RA treated with this JAK inhibitor observed in clinical trials is translated into effectiveness in clinical practice, with a low rate of discontinuations.

Systematic Literature Review of Real-World Evidence on Baricitinib for the Treatment of Rheumatoid Arthritis.

INTRODUCTION: Baricitinib, an orally available small-molecule inhibitor of Janus kinase (JAK)1 and JAK2, is indicated to treat active moderate-to-severe rheumatoid arthritis (RA). OBJECTIVE: This systematic review described the real-world clinical characteristics of baricitinib-treated patients with RA, prescription patterns, effectiveness, drug persistence, patient-reported outcomes (PROs; physical function, pain, health-related quality of life [HRQoL]), patient global assessment (PGA), and safety of baricitinib. METHODS: A PRISMA systematic review of real-world studies was conducted to identify relevant literature published between January 2016 and September 2022 using MEDLINE®, EMBASE®, and evidence-based medicine review databases. Websites or online repositories of the American College of Rheumatology and the European Alliance of Associations for Rheumatology were searched manually to include relevant abstracts from conferences held between January 2016 and November 2022. RESULTS: A total of 11,472 records were identified by searching online databases. Seventy studies were included in the study, of which 40 were abstracts. Most patients were older (51-71 years), female, and with mean RA duration of 4-19 years. Baricitinib was mostly used after the failure of one or more bDMARDs, and 4 mg dosing was prevalent in patients with RA (range 22-100%). Clinical effectiveness of baricitinib was reported in real-world settings regardless of prior biologic/targeted synthetic disease-modifying antirheumatic drug (DMARD) use and concomitant conventional synthetic DMARD use. Achievement of Clinical Disease Activity Index (CDAI) remission was reported in 8.7-60% of patients at week 12 and CDAI low disease activity (LDA) in 20.2-81.6% at week 24. The proportion of patients attaining Simple Disease Activity Index (SDAI) remission was reported in 12% at week 4 to 45.4% at 24 weeks. Drug persistence was high, similar, or equal to anti-tumor necrosis factor drugs. No new safety signals were identified. CONCLUSION: Baricitinib demonstrated effectiveness in the real-world setting with a consistent safety profile observed in clinical studies. Better persistence rates for baricitinib compared to bDMARDs with improvement in PROs were reported, although baricitinib-treated patients had RA with poor prognostic characteristics.

Comparative Effectiveness of First-Line Baricitinib in Patients With Rheumatoid Arthritis in the Australian OPAL Data Set.

OBJECTIVE: To analyze comparative treatment persistence for first-line baricitinib (BARI) versus first-line tumor necrosis factor inhibitor (TNFi) in patients with rheumatoid arthritis (RA) and for first-line BARI initiated as monotherapy versus first-line BARI initiated with at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD). METHODS: Patients with RA who initiated BARI or TNFi as first-line biologic or targeted synthetic DMARD from October 1, 2015, to September 30, 2021, were identified in the OPAL data set. Drug survival times to 6, 12, and 24 months were analyzed using restricted mean survival time (RMST). Multiple imputation and inverse probability of treatment weighting were used to address missing data and nonrandom treatment assignment. RESULTS: A total of 545 patients initiated first-line BARI, including 118 as monotherapy and 427 as csDMARD combination therapy. Three thousand five hundred patients initiated first-line TNFi. There was no difference in drug survival to 6 or 12 months for BARI compared with TNFi; differences in RMST were 0.02 months (95% CI: -0.08 to 0.013; P = 0.65) and 0.31 months (95% CI: -0.02 to 0.63; P = 0.06), respectively. Patients in the BARI group had 1.00 month (95% CI: 0.14 to 1.86; P = 0.02) longer drug survival to 24 months. There was no difference in drug survival for BARI monotherapy compared with combination therapy, with differences in RMST to 6, 12, and 24 months of -0.19 months (95% CI: -0.50 to 0.12; P = 0.12), -0.35 months (95% CI: -1.17 to 0.42; P = 0.41), and -0.56 months (95% CI: -2.66 to 1.54; P = 0.60), respectively. CONCLUSION: In this comparative analysis, treatment persistence up to 24 months was significantly longer for first-line BARI compared with TNFi, but the effect size of 1.00 month is not clinically meaningful. There was no difference in persistence for BARI monotherapy versus combination therapy.

Baricitinib Safety for Events of Special Interest in Populations at Risk: Analysis from Randomised Trial Data Across Rheumatologic and Dermatologic Indications.

INTRODUCTION: Baricitinib, a Janus kinase (JAK) 1/2 inhibitor, is an approved treatment for rheumatoid arthritis (RA), atopic dermatitis (AD), and alopecia areata (AA). Further characterisation of adverse events of special interest (AESI) for JAK inhibitors in at-risk populations will improve benefit-risk assessment for individual patients and diseases. METHODS: Data were pooled from clinical trials and long-term extensions in moderate-to-severe active RA, moderate-to-severe AD, and severe AA. Incidence rates (IR) per 100 patient-years of major adverse cardiovascular event (MACE), malignancy, venous thromboembolism (VTE), serious infection, and mortality were calculated for patients with low risk (younger than 65 years with no specified risk factors), and patients at risk (≥ 1 of: aged 65 years or older, atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, current smoking, HDL cholesterol < 40 mg/dL, BMI ≥ 30 kg/m2, poor mobility on EQ-5D, or history of malignancy). RESULTS: Datasets included baricitinib exposure up to 9.3 years with 14,744 person-years of exposure (PYE) (RA), 3.9 years with 4628 PYE (AD), and 3.1 years with 1868 PYE (AA). In patients with low risk (RA: 31%, AD: 48%, AA: 49%), IRs for MACE (0.05, 0.04, 0), malignancies (0.20, 0.13, 0), VTE (0.09, 0.04, 0), serious infection (1.73, 1.18, 0.6), and mortality (0.04, 0, 0) in the RA, AD, and AA datasets, respectively, were low. In patients at risk (RA: 69%, AD: 52%, AA: 51%), IRs were for MACE (0.70, 0.25, 0.10), malignancies (1.23, 0.45, 0.31), VTE (0.66, 0.12, 0.10), serious infection (2.95, 2.30, 1.05), and mortality (0.78, 0.16, 0) for RA, AD, and AA datasets, respectively. CONCLUSION: Populations with low risk have low incidence of the examined JAK inhibitor-related AESI. In the dermatologic indications, incidence is also low for patients at risk. Considering individual disease burden, risk factors, and response to treatment is relevant to make informed decisions for individual patients treated with baricitinib.