Plivensia (sirukumab) / J&J - LARVOL DELTA

The Efficacy Of Targeted Therapies In Giant Cell Arteritis: A Systematic Review and Meta-Analysis (ACR Convergence 2025) - "SR rates were significantly higher compared to placebo in the patients who received tocilizumab (tocilizumab IV RR(CI 1.90 (1.01-3.56), tocilizumab SC 1.45 (1-06-1.99)), mavrilumab (RR (CI) 1.67(1.12-2.47)), secukinumab (RR(CI): 7.41 (1.89-29.02)) and upadacitinib 15 mg (RR (CI) 1.58 (1.14-2.17). Tocilizumab, mavrilumab, secukinumab and upadacitinib appear to increase the rate of 52-week sustained remission rate. Sarilumab and sirukumab has not shown significant efficacy."

Retrospective data • Review • Giant Cell Arteritis • Immunology

A Systematic Literature Review to Inform the 2025 EULAR Recommendations for Management of Polymyalgia Rheumatica and Large Vessel Vasculitis: Management of Disease Including Relapse and Complications (ACR Convergence 2025) - "RCTs of GCA (low RoB) reported superiority of secukinumab (Phase-2, n=1), mavrilimumab (Phase-2, n=1) and upadacitinib (Phase-3, n=1) vs placebo; Phase-2 trials of sarilumab (n=1) and sirukumab (n=1) were prematurely terminated (high RoB)...RCTs of TAK reported similar effectiveness of methotrexate or mycophenolate (unclear RoB), and superiority of adalimumab vs tocilizumab (high RoB). Phase-3 RCTs in PMR revealed superiority of tocilizumab and sarilumab (low RoB) vs. placebo while smaller phase-2 studies provided initial evidence for efficacy of rituximab (low RoB) and abatacept (unclear RoB) vs placebo (Table 1). A RCT showed similar efficacy of tofacitinib or glucocorticoids in PMR although this study was at high risk of bias. The SLR identified several new Phase-2 and Phase-3 RCTs about the efficacy and safety of IL-6i, IL-17i, Janus kinase inhibitors and B-cell depletion therapies in GCA and PMR. The SLR identified several new Phase-2 and Phase-3 RCTs about the..."

Review • Fatigue • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology • Vasculitis

A SYSTEMATIC LITERATURE REVIEW TO INFORM THE 2025 EULAR RECOMMENDATIONS FOR MANAGEMENT OF POLYMYALGIA RHEUMATICA AND LARGE VESSEL VASCULITIS: MANAGEMENT OF DISEASE INCLUDING RELAPSE AND COMPLICATIONS (EULAR 2025) - "RCTs of GCA (low RoB) reported superiority of secukinumab (Phase-2, n=1), mavrilimumab (Phase-2, n=1) and upadacitinib (Phase-3, n=1) vs placebo; Phase-2 trials of sarilumab (n=1) and sirukumab (n=1) were prematurely terminated (high RoB)...RCTs of TAK reported similar effectiveness of methotrexate or mycophenolate (unclear RoB), and superiority of adalimumab vs tocilizumab (high RoB). Phase-3 RCTs in PMR revealed superiority of tocilizumab and sarilumab (low RoB) vs. placebo while smaller phase-2 studies provided initial evidence for efficacy of rituximab (low RoB) and abatacept (unclear RoB) vs placebo (Table 1). A RCT showed similar efficacy of tofacitinib or glucocorticoids in PMR although this study was at high risk of bias... The systematic review identified several new Phase-2 and Phase-3 RCTs about the efficacy and safety of IL-6i, IL-17i, Janus kinase inhibitors and B-cell depletion therapies in GCA and PMR. High quality adequately sized RCTs in TAK are still..."

Review • Fatigue • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology • Vasculitis

Pharmacodynamic, prognostic, and predictive biomarkers in severe and critical COVID-19 patients treated with sirukumab. (PubMed, Sci Rep) - P2 | "These data suggest that patients with critical COVID-19 without detectable sirukumab-induced IL-4 levels are more likely to benefit from sirukumab treatment. ClinicalTrials.gov Identifier: NCT04380961."

Biomarker • Clinical • Journal • PK/PD data • Infectious Disease • Inflammation • Novel Coronavirus Disease • IL4 • IL6

The IL-6 Hypothesis in COVID-19: A Phase 2, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Free IL-6 Sequestration by the Monoclonal Antibody Sirukumab in Severe and Critical COVID-19. (PubMed, J Infect) - P2 | "In critical COVID-19 patients who received sirukumab, there was no statistically significant difference in time to sustained clinical improvement versus placebo despite objective sequestration of circulating IL-6, questioning IL-6 as a key therapeutic target in COVID-19."

Journal • P2 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IL6

Immune-Targeted Therapies for Depression: Current Evidence for Antidepressant Effects of Monoclonal Antibodies. (PubMed, J Clin Psychiatry) - "Only infliximab and sirukumab were directly examined in individuals with primary depression. mAbs that do not require laboratory monitoring, such as ixekizumab and dupilumab, could hold potential promise if future studies establish their safety profile regarding suicide risk...Further research addressing individuals with more severe depressive symptoms is essential. Direct examination of antidepressant effects of mAbs in people with primary depressive disorders is also crucial to refine their clinical use in the treatment of depression."

Journal • Review • CNS Disorders • Depression • Inflammation • Mood Disorders • Psychiatry

Experimental Medicine Approach for Developing Immunomodulatory Drugs as Novel Treatments for Psychiatric Disorders (ASCP 2024) - "However, subsequent studies of infliximab in bipolar depression and of sirukumab, another monoclonal antibody that targets interleukin 6, have been negative...2. Discuss the potential of monoclonal antibodies as novel antidepressants."

Immunomodulating • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • IL17A • IL6 • TNFA

Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What Have We Learned? (PubMed, BioDrugs) - "Following the termination of the development of sirukumab because of mortality data in early studies, the investigation of olokizumab, which targets a different region of the IL-6 cytokine, has renewed the hope in this area and the safety concerns have been largely alleviated by the open-label extension data. In addition, the efficacy and safety of tocilizumab and sarilumab have led to a rapid investigation of biosimilars and new potent IL-6 receptor blockers. A comprehensive understanding of mechanisms of this pathway with further long-term clinical data and basic research may provide a decisive impact on selecting the appropriate mechanism as the first choice in personalized treatments."

Journal • Review • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • IL6

Drug repurposing analysis for colorectal cancer through network medicine framework: Novel candidate drugs and small molecules. (PubMed, Cancer Invest) - "Based on the gene module, polyethylene glycol, gallic acid, pyrazole, cordycepin, phenothiazine, pantoprazole, cysteamine, indisulam, valinomycin, trametinib, BRD-K81473043, AZD8055, dovitinib, BRD-A17065207, and tyrphostin AG1478 presented as drugs and small molecule candidates previously studied in the CRC. Lornoxicam, suxamethonium, oprelvekin, sirukumab, levetiracetam, sulpiride, NVP-TAE684, AS605240, 480743.cdx, HDAC6 inhibitor ISOX, BRD-K03829970, and L-6307 are proposed as novel drugs and small molecule candidates for CRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • TERC

Role of IL-6 and IL-6 targeted therapy in systemic lupus erythematosus. (PubMed, Rheumatology (Oxford)) - "Currently, there are no studies registered in clinicaltrials.gov to assess the IL-6 targeted therapy in SLE, yet its role in the future remains to be defined. This narrative review analyzes these and potential areas of future studies with IL-6 targeted therapy in SLE."

Journal • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • IL6

[VIRTUAL] Baricitinib in Relapsing Giant Cell Arteritis: A Prospective Open-Label Single-Institution Study (ACR-CONVERGENCE 2021) - "Treatments prior to study entry included: glucocorticoids (15, 100%); methotrexate (2, 13%); cyclophosphamide (1, 7%); sirukumab (1, 7%)...Four (27%) patients entered the study on prednisone 30mg/day, 6 (40%) at 20 mg/day, and 5 (33%) at 10mg/day... In this proof of concept study, baricitinib at a dose of 4mg/day appeared both safe and effective in the management of patients with relapsing GCA. Larger randomized clinical trials are needed to determine the utility of JAK inhibition in GCA."

Clinical • Chronic Kidney Disease • Fatigue • Giant Cell Arteritis • Hematological Disorders • Immunology • Infectious Disease • Nephrology • Novel Coronavirus Disease • Pain • Renal Disease • Thrombocytopenia • CRP • JAK1 • JAK3

Comparative efficacy and safety of biologic agents in patients with active rheumatoid arthritis and inadequate response to tumor necrosis factor inhibitors: A Bayesian network meta-analysis of randomized controlled trials. (PubMed, Int J Clin Pharmacol Ther) - "All biologic agents studied were effective in treating patients with TNF inhibitor-refractory RA; however, tocilizumab, rituximab, and abatacept appeared to be more efficient than sarilumab, sirukumab, and secukinumab. There were no differences between the treatments with respect to safety."

Journal • Retrospective data • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis. (PubMed, Ann Rheum Dis) - "This SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR's RA management recommendation."

Clinical • Journal • Immunology • Rheumatoid Arthritis • Rheumatology

Comparison of the efficacy and safety of tocilizumab, sarilumab, and sirukumab in comparison with adalimumab as monotherapy in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials. (PubMed, Int J Clin Pharmacol Ther) - "Based on ACR20 and ACR50 response rates, monotherapy with tocilizumab 8 mg, followed by sarilumab and sirukumab monotherapy, was optimal for patients with RA responding inadequately to MTX or showing intolerance."

Journal • Monotherapy • Retrospective data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical Confirmed Coronavirus Disease (COVID)-19 (clinicaltrials.gov) - P2; N=212; Completed; Sponsor: Janssen Pharmaceutica N.V., Belgium; Active, not recruiting ➔ Completed

Clinical • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • PCR

Impact of Interferons and Biological Drug Inhibitors of IL-2 and IL-6 on Small-Molecule Drug Metabolism Through the Cytochrome P450 System. (PubMed, Ann Pharmacother) - "Exogenous interferons suppress CYP1A2 (theophylline, caffeine, antipyrone) clearance by 20% to 49% in patients; have minimal impact on CYP3A4 (midazolam and dapsone), CYP2C9 (tolbutamide), or CYP2C19 (mephenytoin) metabolism; and increase CYP2D6 (debrisoquine, dextromethorphan) metabolism. Biological IL-2 inhibitors (basiliximab, daclizumab) have no effect on metabolism via CYP1A2 (caffeine), CYP2C9 (s-warfarin), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), and CYP3A4 (midazolam, tacrolimus) but may enhance CYP3A4 (cyclosporin) metabolism over time. IL-6 inhibitors (sirukumab, tocilizumab, sarilumab) significantly enhance metabolism via CYP2C9 (s-warfarin), CYP2C19 (omeprazole), and CYP3A4 (simvastatin, midazolam) and reduce metabolism via CYP1A2 (caffeine)...In clinical practice, clinicians may consider these metabolic changes as an additive effect to a patient's entire disease and medication profile when determining risk/benefit of treatment. Interferon therapy..."

Journal • Immunology • Inflammation • CYP1A2 • CYP2C19 • CYP2C9 • CYP3A4 • IL2 • IL6

[VIRTUAL] CONFOUNDING EFFECTS OF CONTINUED METHOTREXATE IN PLACEBO ARMS (PLC) OF RHEUMATOID ARTHRITIS (RA) CLINICAL TRIALS – A POST-HOC ANALYSIS OF TWO RANDOMIZED CONTROLLED TRIALS (RCTS) (EULAR 2021) - " To investigate the hypothesis we conducted a post-hoc analysis of two RCTs that allowed inclusion of patients with and without cMTX - the GO-AFTER and the SIRROUND-T trials, investigating golimumab and sirukumab, respectively, compared with PLC in patients who had an insufficient response to biological DMARDs.(1,2) All PLC randomized patients of both trials were pooled and included in the analyses; we did not analyse the active treatment groups. In patients randomized to placebo therapy, continued MTX background therapy increases clinical responses and achievement of good clinical states. These findings imply that pre-existing and putatively insufficient background therapy should be effectively optimized before enrollment into a clinical trial protocol."

Clinical • Retrospective data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical Confirmed Coronavirus Disease (COVID)-19 (clinicaltrials.gov) - P2; N=212; Active, not recruiting; Sponsor: Janssen Pharmaceutica N.V., Belgium; Recruiting ➔ Active, not recruiting; N=111 ➔ 212

Clinical • Enrollment change • Enrollment closed • Infectious Disease • Neutropenia • Novel Coronavirus Disease • Respiratory Diseases • PCR

A Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical Confirmed Coronavirus Disease (COVID)-19 (clinicaltrials.gov) - P2; N=111; Recruiting; Sponsor: Janssen Pharmaceutica N.V., Belgium; N=270 ➔ 111; Trial primary completion date: Sep 2021 ➔ Apr 2021

Clinical • Enrollment change • Trial primary completion date • Infectious Disease • Neutropenia • Novel Coronavirus Disease • Respiratory Diseases • PCR

Comparative effectiveness and safety of non-tumour necrosis factor biologics and Janus kinase inhibitors in patients with active rheumatoid arthritis showing insufficient response to tumour necrosis factor inhibitors: A Bayesian network meta-analysis of randomized controlled trials. (PubMed, J Clin Pharm Ther) - "Both non-TNF biologics and JAK inhibitors have similar effects in patients with active RA that are refractory to anti-TNF treatment, and there were no differences with regard to safety among the treatments."

HEOR • Journal • Retrospective data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Long-term safety and efficacy of sirukumab for patients with rheumatoid arthritis who previously received sirukumab in randomised controlled trials (SIRROUND-LTE). (PubMed, RMD Open) - P3 | "The safety profile of sirukumab in the LTE remained consistent with that reported in SIRROUND-D and SIRROUND-T and efficacy was maintained."

Clinical • Journal • Cardiovascular • Gastrointestinal Disorder • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • IL6 • TNFA

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. (PubMed) - Ann Rheum Dis - "...The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib)...For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies."

Journal • Biosimilar • Immunology • Rheumatoid Arthritis

Late-Stage Failures of Monoclonal Antibody Drugs: A Retrospective Case Study Analysis. (PubMed, Pharmacology) - "By learning from previous mistakes and adhering to the principles and recommendations provided, it is possible to avoid these common pitfalls, increasing the likelihood of success in phase III clinical trials, and thus securing regulatory approval."

Journal • Retrospective data • Review

A Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical Confirmed Coronavirus Disease (COVID)-19 (clinicaltrials.gov) - P2; N=270; Recruiting; Sponsor: Janssen Pharmaceutica N.V., Belgium; Trial primary completion date: Mar 2021 ➔ Sep 2021

Clinical • Trial primary completion date • Infectious Disease • Neutropenia • Novel Coronavirus Disease • PCR

A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Giant Cell Arteritis. (PubMed, Rheumatol Ther) - P3 | "Although data were limited due to early termination and shortened treatment duration, sirukumab treatment resulted in numerically lower proportions of patients with flare by week 52 versus placebo, with no unexpected safety findings."

Clinical • Journal • Giant Cell Arteritis