Evidence map›Paper›PMID 42691741›Full record

Observational studySeminars in arthritis and rheumatism2026

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

Abdurrahman Tufan, Deborah L Stone, Tina Romeo, Patrycja Hoffmann, Lorena Wilson, Natalie T Deuitch, Christina Kozycki, Kalpana Manthiram, Sarah Hansen, Daniel L Kastner and 1 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Seminars in arthritis and rheumatism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Abdurrahman TufanInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; Department of Internal Medicine and Rheumatology, Faculty of Medicine, Gazi University, Ankara, Turkiye. Electronic address: dratufan@hotmail.com.
Deborah L StoneInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: stonedeb@mail.nih.gov.
Tina RomeoInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: tina.romeo@nih.gov.
Patrycja HoffmannInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: patrycja.hoffmann@nih.gov.
Lorena WilsonInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: lorena.wilson@nih.gov.
Natalie T DeuitchInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: natalie.deuitch@nih.gov.
Christina KozyckiInnate Immune Activation Unit, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. Electronic address: christina.kozycki@nih.gov.
Kalpana ManthiramLaboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: kalpana.manthiram@nih.gov.
Sarah HansenInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; Division of Rheumatology, Department of Medicine, The University of British Columbia, Vancouver, Canada. Electronic address: sarah.hansen7@vch.ca.
Daniel L KastnerInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: dan.kastner@nih.gov.
Amanda K OmbrelloInflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: amanda.ombrello@nih.gov.

Funding

Intramural NIH HHS Z99 HG999999
6 · The paper itself

Abstract

objectivesSystemic 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.

methodsIn 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.

resultsThirty-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).

conclusionsACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Indexed as

Biological ProductsHereditary Autoinflammatory DiseasesJanus Kinase InhibitorsAdolescentAdultAgedChildChild, PreschoolDrug Therapy, CombinationFemaleHumansLongitudinal StudiesMaleMiddle AgedRetrospective StudiesTreatment OutcomeBiological ProductsJanus Kinase InhibitorsAdvanced combination therapyAutoinflammatory diseasesCombination targeted treatmentDual biologicDual targeted therapyImmune mediated inflammatory diseaseJAK inhibitors

Identifiers

PMID42691741
PMCPMC13614094

What OpenQuestion holds

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Registered trials

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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.