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Peer-reviewedCC BY 4.0EULAR Rheumatology Open

Sustained pain improvement and IL-12-related biomarker changes in rheumatoid arthritis patients initiating baricitinib or TNF inhibitor therapy

  • Christine Behrendt1
  • Khetam Ghannam1
  • Monika Brunner-Weinzierl2
  • Anke Lux3
  • André Wille4
  • Mandy Gläß4
  • Eugen Feist1,4
4 affiliations
  1. 1Experimental Rheumatology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
  2. 2Experimental Pediatrics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
  3. 3Institute of Medical Data Science, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
  4. 4Rheumatology and Clinical Immunology, Helios Clinic Vogelsang-Gommern, Gommern, Germany
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Abstract

Objectives: The Janus kinase (JAK) inhibitor baricitinib has demonstrated analgesic effects that may extend beyond anti-inflammatory mechanisms. This study investigated longitudinal pain trajectories and their association with interleukin (IL)-6 and IL-12 changes in patients with rheumatoid arthritis (RA) initiating baricitinib or tumour necrosis factor inhibitor (TNFi) therapy.

Methods: In this single-centre prospective study, 60 patients with RA initiating baricitinib (n = 29) or TNFi therapy (n = 31) were followed at baseline, 2 weeks and 3 months. Healthy donors (n = 15) served as a biomarker reference. IL-6, IL-12p40, and IL-12p70 were measured using Enzyme-Linked Immunosorbent Assay (ELISA) and multiplex technology. Pain was assessed using numerical rating scales, and disease activity and function using 28-joint Disease Activity Score–erythrocyte sedimentation rate and Health Assessment Questionnaire Disability Index. Analyses were within-group and exploratory; adjusted mixed-effects models assessed between-group trajectories.

Results: Within both groups, disease activity, function, and all 3 pain domains improved significantly over 3 months. Under baricitinib, average pain and swollen joint count (SJC) improved further between 2 weeks and 3 months, whereas TNFi showed earlier improvement at 2 weeks. IL-6, IL-12p40, and IL-12p70 showed within-group reductions under baricitinib, reaching significance at 3 months. Adjusted models showed no robust between-group differences.

Conclusions: In this small prospective pilot cohort, both therapies were associated with early, clinically relevant pain improvement, with continued improvement in average pain and SJC under baricitinib. This sustained response was accompanied by within-group reductions in IL-6 and, notably, the IL-12 subunits, a JAK/tyrosine kinase(TYK)-linked pathway that has been less explored in relation to RA pain. These exploratory observations are hypothesis-generating and warrant confirmation in larger, adequately powered studies.

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Cite

BibTeXRIS
BibTeX
@article{behrendt2026sustained,
  title = {{Sustained pain improvement and IL-12-related biomarker changes in rheumatoid arthritis patients initiating baricitinib or TNF inhibitor therapy}},
  author = {Christine Behrendt and Khetam Ghannam and Monika Brunner-Weinzierl and Anke Lux and André Wille and Mandy Gläß and Eugen Feist},
  journal = {EULAR Rheumatology Open},
  year = {2026},
  month = oct,
  doi = {10.1016/j.ero.2026.100259},
  url = {https://doi.org/10.1016/j.ero.2026.100259},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Sustained pain improvement and IL-12-related biomarker changes in rheumatoid arthritis patients initiating baricitinib or TNF inhibitor therapy
AU  - Christine Behrendt
AU  - Khetam Ghannam
AU  - Monika Brunner-Weinzierl
AU  - Anke Lux
AU  - André Wille
AU  - Mandy Gläß
AU  - Eugen Feist
PY  - 2026
DA  - 2026/10/19
JO  - EULAR Rheumatology Open
DO  - 10.1016/j.ero.2026.100259
UR  - https://doi.org/10.1016/j.ero.2026.100259
AB  - Objectives: The Janus kinase (JAK) inhibitor baricitinib has demonstrated analgesic effects that may extend beyond anti-inflammatory mechanisms. This study investigated longitudinal pain trajectories and their association with interleukin (IL)-6 and IL-12 changes in patients with rheumatoid arthritis (RA) initiating baricitinib or tumour necrosis factor inhibitor (TNFi) therapy.  Methods: In this single-centre prospective study, 60 patients with RA initiating baricitinib (n = 29) or TNFi therapy (n = 31) were followed at baseline, 2 weeks and 3 months. Healthy donors (n = 15) served as a biomarker reference. IL-6, IL-12p40, and IL-12p70 were measured using Enzyme-Linked Immunosorbent Assay (ELISA) and multiplex technology. Pain was assessed using numerical rating scales, and disease activity and function using 28-joint Disease Activity Score–erythrocyte sedimentation rate and Health Assessment Questionnaire Disability Index. Analyses were within-group and exploratory; adjusted mixed-effects models assessed between-group trajectories.  Results: Within both groups, disease activity, function, and all 3 pain domains improved significantly over 3 months. Under baricitinib, average pain and swollen joint count (SJC) improved further between 2 weeks and 3 months, whereas TNFi showed earlier improvement at 2 weeks. IL-6, IL-12p40, and IL-12p70 showed within-group reductions under baricitinib, reaching significance at 3 months. Adjusted models showed no robust between-group differences.  Conclusions: In this small prospective pilot cohort, both therapies were associated with early, clinically relevant pain improvement, with continued improvement in average pain and SJC under baricitinib. This sustained response was accompanied by within-group reductions in IL-6 and, notably, the IL-12 subunits, a JAK/tyrosine kinase(TYK)-linked pathway that has been less explored in relation to RA pain. These exploratory observations are hypothesis-generating and warrant confirmation in larger, adequately powered studies.
SN  - 3050-7081
ER  -