Biologic–biologic and biologic–JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.
Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephaliti...
| Published in: | Seminars in Arthritis & Rheumatism Vol. 80 |
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| Main Authors: | , , , , , , , , , , |
| Format: | research Journal Article |
| Published: |
W B Saunders
Oct2026
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=196797920&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 196797920 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00490172 4GQ jtl: Seminars in Arthritis & Rheumatism issn: 00490172 maglogo: N pubinfo: dt: Oct2026 vid: 80 pid: 1351 pub: W B Saunders place: Philadelphia, Pennsylvania artinfo: ui: 196797920 196797920 196797920 10.1016/j.semarthrit.2026.153067 196797920 ppct: 1 formats: tig: atl: Biologic–biologic and biologic–JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases. aug: au: Tufan, Abdurrahman Stone, Deborah L. Romeo, Tina Hoffmann, Patrycja Wilson, Lorena Deuitch, Natalie T. Kozycki, Christina Manthiram, Kalpana Hansen, Sarah Kastner, Daniel L. Ombrello, Amanda K. affil: Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA sug: subj: Hereditary Autoinflammatory Diseases Drug Therapy Biological Products Therapeutic Use Janus Kinase Inhibitors Therapeutic Use Drug Therapy, Combination Human Male Female Child, Preschool Child Adolescence Adult Middle Age Aged Nonexperimental Studies Retrospective Design Record Review Prospective Studies Immunosuppressive Agents Treatment Outcomes Mevalonate Kinase Deficiency Drug Therapy Reactive Arthritis Drug Therapy C-Reactive Protein Glucocorticoids Descriptive Statistics Child, Preschool: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Male Female ab: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. Thirty-eight patients (median age 30 years [range 4–76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11–186). ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain. [Display omitted] pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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