Pain and inflammation as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis: a mediation analysis
<p><strong>Introduction:</strong> Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Using mediation modelling, we describe interrelationships between fatigue, pain, morning stiffness, C-reactive protein (CRP) and tofacitinib treatm...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer
2023
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| _version_ | 1797110427542355968 |
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| author | Kristensen, LE Navarro-Compán, V Magrey, M Bushmakin, AG Cappelleri, JC Yndestad, A Dina, O Taylor, PC |
| author_facet | Kristensen, LE Navarro-Compán, V Magrey, M Bushmakin, AG Cappelleri, JC Yndestad, A Dina, O Taylor, PC |
| author_sort | Kristensen, LE |
| collection | OXFORD |
| description | <p><strong>Introduction:</strong> Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Using mediation modelling, we describe interrelationships between fatigue, pain, morning stiffness, C-reactive protein (CRP) and tofacitinib treatment in patients with AS.</p>
<p><strong>Methods:</strong> Data from phase 2 (NCT01786668)/phase 3 (NCT03502616) studies of patients receiving tofacitinib 5 mg twice daily (BID) or placebo were used. Initial models included treatment as the independent binary variable (tofacitinib 5 mg BID versus placebo); fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F; model A] or Bath AS Disease Activity Index [BASDAI] Q1 [model B]) as the dependent variable; and pain (total back pain/nocturnal spinal pain [model A] or pain measured by BASDAI Q2/3 [model B]), morning stiffness (BASDAI Q5/6) and CRP as mediator variables.</p>
<p><strong>Results:</strong> Pooled data from 370/371 patients were included in models A/B. Initial models demonstrated that tofacitinib treatment affects fatigue mainly indirectly via pain and morning stiffness. As a result, initial models were respecified to exclude direct treatment effect and the indirect effect via CRP. For respecified model A, 44.0% of the indirect effect of tofacitinib treatment on fatigue was mediated via back pain/morning stiffness, 40.0% via morning stiffness alone and 16.0% via back pain alone (all <em>P</em> < 0.05). For respecified model B, 80.8% of the indirect effect of tofacitinib treatment on fatigue was mediated via pain/morning stiffness and 19.2% via pain alone (both <em>P</em> < 0.05).</p>
<p><strong>Conclusions:</strong> In tofacitinib-treated patients with AS, improvements in fatigue were collectively mediated through combined treatment effects on morning stiffness and pain.</p> |
| first_indexed | 2024-03-07T07:54:42Z |
| format | Journal article |
| id | oxford-uuid:8a9200dd-6e34-46e0-8d4d-f27ae8a953f4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:54:42Z |
| publishDate | 2023 |
| publisher | Springer |
| record_format | dspace |
| spelling | oxford-uuid:8a9200dd-6e34-46e0-8d4d-f27ae8a953f42023-08-07T08:24:20ZPain and inflammation as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis: a mediation analysisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8a9200dd-6e34-46e0-8d4d-f27ae8a953f4EnglishSymplectic ElementsSpringer2023Kristensen, LENavarro-Compán, VMagrey, MBushmakin, AGCappelleri, JCYndestad, ADina, OTaylor, PC<p><strong>Introduction:</strong> Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Using mediation modelling, we describe interrelationships between fatigue, pain, morning stiffness, C-reactive protein (CRP) and tofacitinib treatment in patients with AS.</p> <p><strong>Methods:</strong> Data from phase 2 (NCT01786668)/phase 3 (NCT03502616) studies of patients receiving tofacitinib 5 mg twice daily (BID) or placebo were used. Initial models included treatment as the independent binary variable (tofacitinib 5 mg BID versus placebo); fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F; model A] or Bath AS Disease Activity Index [BASDAI] Q1 [model B]) as the dependent variable; and pain (total back pain/nocturnal spinal pain [model A] or pain measured by BASDAI Q2/3 [model B]), morning stiffness (BASDAI Q5/6) and CRP as mediator variables.</p> <p><strong>Results:</strong> Pooled data from 370/371 patients were included in models A/B. Initial models demonstrated that tofacitinib treatment affects fatigue mainly indirectly via pain and morning stiffness. As a result, initial models were respecified to exclude direct treatment effect and the indirect effect via CRP. For respecified model A, 44.0% of the indirect effect of tofacitinib treatment on fatigue was mediated via back pain/morning stiffness, 40.0% via morning stiffness alone and 16.0% via back pain alone (all <em>P</em> < 0.05). For respecified model B, 80.8% of the indirect effect of tofacitinib treatment on fatigue was mediated via pain/morning stiffness and 19.2% via pain alone (both <em>P</em> < 0.05).</p> <p><strong>Conclusions:</strong> In tofacitinib-treated patients with AS, improvements in fatigue were collectively mediated through combined treatment effects on morning stiffness and pain.</p> |
| spellingShingle | Kristensen, LE Navarro-Compán, V Magrey, M Bushmakin, AG Cappelleri, JC Yndestad, A Dina, O Taylor, PC Pain and inflammation as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis: a mediation analysis |
| title | Pain and inflammation as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis: a mediation analysis |
| title_full | Pain and inflammation as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis: a mediation analysis |
| title_fullStr | Pain and inflammation as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis: a mediation analysis |
| title_full_unstemmed | Pain and inflammation as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis: a mediation analysis |
| title_short | Pain and inflammation as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis: a mediation analysis |
| title_sort | pain and inflammation as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis a mediation analysis |
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