ReviewFrontiers in cell and developmental biology2021
Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects.
Review in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
149 citing papers in PubMed, 2 syntheses or guidelines pooled it, 237 citations in OpenAlex.
- Cardiovascular Challenges in Chronic Lymphocytic Leukemia (CLL) Patients Undergoing Bruton Tyrosine Kinase (BTK) Inhibitor Therapy.European journal of haematology · 2026Pooled it
- Efficacy and safety of first- versus second-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Pharmacology and safety of TAS5315, a Bruton tyrosine kinase inhibitor, in healthy volunteers: First-in-human, randomized, ascending-dose studies.British journal of clinical pharmacology · 2025Trial
- Prospective phase II trial of first-line rituximab, methotrexate, and orelabrutinib (R-MO) in primary central nervous system lymphoma.Blood cancer journal · 2025Trial
- Acquired mutations in patients with relapsed/refractory CLL who progressed in the ALPINE study.Blood advances · 2025Trial
- Pirtobrutinib monotherapy in Bruton tyrosine kinase inhibitor-intolerant patients with B-cell malignancies: results of the phase I/II BRUIN trial.Haematologica · 2025Trial
- Safety, pharmacokinetics, and pharmacodynamics of sofnobrutinib, a novel non-covalent BTK inhibitor, in healthy subjects: First-in-human phase I study.Clinical and translational science · 2024Trial
- A prospective study of zanubrutinib, a Bruton tyrosine kinase inhibitor, in relapsed/refractory idiopathic multicentric Castleman disease.International journal of hematology · 2024Trial
- Efficacy and safety results after >3.5 years of treatment with the Bruton's tyrosine kinase inhibitor evobrutinib in relapsing multiple sclerosis: Long-term follow-up of a Phase II randomised clinical trial with a cerebrospinal fluid sub-study.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024Trial
- Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program.American journal of clinical dermatology · 2024Trial
- Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjögren's syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial.Annals of the rheumatic diseases · 2024Trial
- A phase II study of Bruton's tyrosine kinase inhibition for the prevention of anaphylaxis.The Journal of clinical investigation · 2023Trial
- Characterisation of the safety profile of evobrutinib in over 1000 patients from phase II clinical trials in multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus: an integrated safety analysis.Journal of neurology, neurosurgery, and psychiatry · 2023Trial
- Two-year outcomes of tirabrutinib monotherapy in Waldenström's macroglobulinemia.Cancer science · 2022Trial
- Optic nerve infiltration in chronic lymphocytic leukemia treated with acalabrutinib monotherapy: A case report.American journal of ophthalmology case reports · 2026Article
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Monovalent Anti-FcγRIIA Antibody Blocks Immune-Mediated Thrombocytopenia and Thrombosis With Minimal Adverse Side Effects in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Safety and Management of Targeted Therapies for Relapsed/Refractory Chronic Lymphocytic Leukemia.Drug safety · 2026Review
- Comparative atrial fibrillation risk across Bruton's tyrosine kinase inhibitors in B-cell malignancies: A nationwide population-based study.British journal of haematology · 2026Article
- Review
89 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytoplasmic protein-tyrosine kinase BTK plays an essential role for differentiation and survival of B-lineage cells and, hence, represents a suitable drug target. The number of BTK inhibitors (BTKis) in the clinic has increased considerably and currently amounts to at least 22. First-in-class was ibrutinib, an irreversible binder forming a covalent bond to a cysteine in the catalytic region of the kinase, for which we have identified 228 active trials listed at ClinicalTrials.gov. Next-generation inhibitors, acalabrutinib and zanubrutinib, are approved both in the United States and in Europe, and zanubrutinib also in China, while tirabrutinib is currently only registered in Japan. In most cases, these compounds have been used for the treatment of B-lymphocyte tumors. However, an increasing number of trials instead addresses autoimmunity and inflammation in multiple sclerosis, rheumatoid arthritis, pemphigus and systemic lupus erythematosus with the use of either irreversibly binding inhibitors, e.g., evobrutinib and tolebrutinib, or reversibly binding inhibitors, like fenebrutinib. Adverse effects (AEs) have predominantly implicated inhibition of other kinases with a BTKi-binding cysteine in their catalytic domain. Analysis of the reported AEs suggests that ibrutinib-associated atrial fibrillation is caused by binding to ERBB2/HER2 and ERBB4/HER4. However, the binding pattern of BTKis to various additional kinases does not correlate with the common assumption that skin manifestations and diarrhoeas are off-target effects related to EGF receptor inhibition. Moreover, dermatological toxicities, diarrhoea, bleedings and invasive fungal infections often develop early after BTKi treatment initiation and subsequently subside. Conversely, cardiovascular AEs, like hypertension and various forms of heart disease, often persist.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.