Identifying and quantifying the role of inflammation in pain reduction for patients with psoriatic arthritis treated with tofacitinib: a mediation analysis
<p><strong>Introduction: </strong>Pain is a multidimensional factor and core domain of psoriatic arthritis (PsA). This analysis aimed to quantify the role of potential inflammation-associated outcomes on pain reduction in patients with PsA receiving tofacitinib, using medi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer
2022
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| _version_ | 1826309570281078784 |
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| author | de Vlam, K Mease, PJ Bushmakin, AG Fleischmann, R Ogdie, A Azevedo, VF Merola, JF Woolcott, J Cappelleri, JC Fallon, L Taylor, PC |
| author_facet | de Vlam, K Mease, PJ Bushmakin, AG Fleischmann, R Ogdie, A Azevedo, VF Merola, JF Woolcott, J Cappelleri, JC Fallon, L Taylor, PC |
| author_sort | de Vlam, K |
| collection | OXFORD |
| description | <p><strong>Introduction: </strong>Pain is a multidimensional factor and core domain of psoriatic arthritis (PsA). This analysis aimed to quantify the role of potential inflammation-associated outcomes on pain reduction in patients with PsA receiving tofacitinib, using mediation modeling.</p>
<p><strong>Methods: </strong>Pooled data were from two phase 3 studies (OPAL Broaden and OPAL Beyond) of patients with active PsA treated with tofacitinib 5 mg twice daily or placebo. Mediation modeling was utilized to quantify the indirect effects (via Itch Severity Item [ISI], C-reactive protein [CRP] levels, swollen joint count [SJC], Psoriasis Area and Severity Index [PASI], and enthesitis [using Leeds Enthesitis Index]) and direct effects (representing all other factors) of tofacitinib treatment on pain improvement.</p>
<p><strong>Results: </strong>The initial model showed that tofacitinib treatment affects pain, primarily indirectly, via ISI, CRP, SJC, PASI, and enthesitis (overall 84.0%; <em>P</em> = 0.0009), with 16.0% (<em>P</em> = 0.5274) attributable to the direct effect. The model was respecified to exclude SJC and PASI. Analysis of the final model revealed that 29.5% (<em>P</em> = 0.0579) of tofacitinib treatment effect on pain was attributable to the direct effect, and 70.5% (<em>P</em> < 0.0001) was attributable to the indirect effect. ISI, CRP, and enthesitis mediated 37.4% (<em>P</em> = 0.0002), 15.3% (<em>P</em> = 0.0107), and 17.8% (<em>P</em> = 0.0157) of the tofacitinib treatment effect on pain, respectively.</p>
<p><strong>Conclusions: </strong>The majority of the effect of tofacitinib on pain was collectively mediated by itch, CRP, and enthesitis, with itch being the primary mediator of treatment effect.</p>
<p><strong>Trial Registration</strong>: NCT01877668, NCT01882439.</p> |
| first_indexed | 2024-03-07T07:37:45Z |
| format | Journal article |
| id | oxford-uuid:45efe8b8-871d-443a-b55c-32374795f3db |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:37:45Z |
| publishDate | 2022 |
| publisher | Springer |
| record_format | dspace |
| spelling | oxford-uuid:45efe8b8-871d-443a-b55c-32374795f3db2023-03-22T15:14:58ZIdentifying and quantifying the role of inflammation in pain reduction for patients with psoriatic arthritis treated with tofacitinib: a mediation analysisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:45efe8b8-871d-443a-b55c-32374795f3dbEnglishSymplectic ElementsSpringer2022de Vlam, KMease, PJBushmakin, AGFleischmann, ROgdie, AAzevedo, VFMerola, JFWoolcott, JCappelleri, JCFallon, LTaylor, PC<p><strong>Introduction: </strong>Pain is a multidimensional factor and core domain of psoriatic arthritis (PsA). This analysis aimed to quantify the role of potential inflammation-associated outcomes on pain reduction in patients with PsA receiving tofacitinib, using mediation modeling.</p> <p><strong>Methods: </strong>Pooled data were from two phase 3 studies (OPAL Broaden and OPAL Beyond) of patients with active PsA treated with tofacitinib 5 mg twice daily or placebo. Mediation modeling was utilized to quantify the indirect effects (via Itch Severity Item [ISI], C-reactive protein [CRP] levels, swollen joint count [SJC], Psoriasis Area and Severity Index [PASI], and enthesitis [using Leeds Enthesitis Index]) and direct effects (representing all other factors) of tofacitinib treatment on pain improvement.</p> <p><strong>Results: </strong>The initial model showed that tofacitinib treatment affects pain, primarily indirectly, via ISI, CRP, SJC, PASI, and enthesitis (overall 84.0%; <em>P</em> = 0.0009), with 16.0% (<em>P</em> = 0.5274) attributable to the direct effect. The model was respecified to exclude SJC and PASI. Analysis of the final model revealed that 29.5% (<em>P</em> = 0.0579) of tofacitinib treatment effect on pain was attributable to the direct effect, and 70.5% (<em>P</em> < 0.0001) was attributable to the indirect effect. ISI, CRP, and enthesitis mediated 37.4% (<em>P</em> = 0.0002), 15.3% (<em>P</em> = 0.0107), and 17.8% (<em>P</em> = 0.0157) of the tofacitinib treatment effect on pain, respectively.</p> <p><strong>Conclusions: </strong>The majority of the effect of tofacitinib on pain was collectively mediated by itch, CRP, and enthesitis, with itch being the primary mediator of treatment effect.</p> <p><strong>Trial Registration</strong>: NCT01877668, NCT01882439.</p> |
| spellingShingle | de Vlam, K Mease, PJ Bushmakin, AG Fleischmann, R Ogdie, A Azevedo, VF Merola, JF Woolcott, J Cappelleri, JC Fallon, L Taylor, PC Identifying and quantifying the role of inflammation in pain reduction for patients with psoriatic arthritis treated with tofacitinib: a mediation analysis |
| title | Identifying and quantifying the role of inflammation in pain reduction for patients with psoriatic arthritis treated with tofacitinib: a mediation analysis |
| title_full | Identifying and quantifying the role of inflammation in pain reduction for patients with psoriatic arthritis treated with tofacitinib: a mediation analysis |
| title_fullStr | Identifying and quantifying the role of inflammation in pain reduction for patients with psoriatic arthritis treated with tofacitinib: a mediation analysis |
| title_full_unstemmed | Identifying and quantifying the role of inflammation in pain reduction for patients with psoriatic arthritis treated with tofacitinib: a mediation analysis |
| title_short | Identifying and quantifying the role of inflammation in pain reduction for patients with psoriatic arthritis treated with tofacitinib: a mediation analysis |
| title_sort | identifying and quantifying the role of inflammation in pain reduction for patients with psoriatic arthritis treated with tofacitinib a mediation analysis |
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