Pain and Inflammation as Mediators of Tofacitinib Treatment Effect on Fatigue in Patients with Ankylosing Spondylitis: A Mediation Analysis (original) (raw)
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RMD Open, 2022
Van den Bosch F, et al. Effect of tofacitinib on pain, fatigue, health-related quality of life and work productivity in patients with active ankylosing spondylitis: results from a phase III, randomised, double-blind, placebocontrolled trial.
Rheumatology and Therapy
Introduction: 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. Methods: 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. Results: The initial model showed that tofacitinib treatment affects pain, primarily indirectly, via ISI, CRP, SJC, PASI, and enthesitis (overall 84.0%; P = 0.0009), with 16.0% (P = 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% (P = 0.0579) of tofacitinib treatment effect on pain was attributable to the direct effect, and 70.5% (P \ 0.0001) was attributable to the indirect effect. ISI, CRP, and enthesitis mediated 37.4% (P = 0.0002), 15.3% (P = 0.0107), and 17.8% (P = 0.0157) of the tofacitinib treatment effect on pain, respectively.
RMD Open
ObjectivePost hoc analysis of pooled data from nine randomised controlled trials to assess the effect of tofacitinib (oral Janus kinase inhibitor for treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA)) on residual pain in patients with RA or PsA with abrogated inflammation.MethodsPatients who received ≥1 dose of tofacitinib 5 mg twice daily, adalimumab or placebo with/without background conventional synthetic disease-modifying antirheumatic drugs and had abrogated inflammation (swollen joint count (SJC)=0 and C reactive protein (CRP)<6 mg/L) after 3 months’ therapy were included. Assessments included Patient’s Assessment of Arthritis Pain at month 3 (Visual Analogue Scale [VAS] 0–100 mm). Scores were summarised descriptively; treatment comparisons assessed by Bayesian network meta-analyses (BNMA).ResultsFrom the total population with RA/PsA, 14.9% (382 of 2568), 17.1% (118 of 691) and 5.5% (50 of 909) of patients receiving tofacitinib, adalimumab and placebo, re...
Rheumatology and Therapy, 2019
Introduction: Ixekizumab, a humanized interleukin-17A antibody, has shown efficacy in ankylosing spondylitis (AS), with a greater proportion of ixekizumab-treated patients achieving an ASAS40 (Assessment of Spondyloarthritis International Society 40) endpoint compared to placebo. An ASAS40 response is a high standard that is not routinely used in clinical practice. The goals of this study were (a) to measure improvement in ixekizumab-treated patients in the four ASAS treatment response domains and in other patient-reported outcomes, and (b) to determine how the ASAS response was associated with changes in spinal pain at night, fatigue, sleep, and the Short Form 36-Item Physical Component Summary (SF-36 PCS). Methods: The COAST-V and COAST-W trials were randomized, double-blind, controlled trials examining ixekizumab efficacy in patients with AS who were biologic disease-modifying
Rheumatology and Therapy, 2020
Introduction: Patients with ankylosing spondylitis (AS) are burdened with symptoms impacting work productivity measured by presenteeism, absenteeism, overall work impairment, and activity impairment. Ixekizumab, a high-affinity monoclonal antibody selectively targeting interleukin-17A, has been demonstrated to improve disease signs and symptoms in two phase 3 trials of AS. This study investigated for 52 weeks the effect of ixekizumab treatment on work productivity in patients with active AS. Methods: COAST-V (NCT02696785) and COAST-W (NCT02696798) were phase 3, multicenter, randomized, controlled trials investigating the efficacy of ixekizumab 80 mg every 4 weeks (Q4W) and every 2 weeks (Q2W) in patients with AS naïve to biologic diseasemodifying antirheumatic drugs (bDMARDs; COAST-V) or who were inadequate responders or intolerant to tumor necrosis factor inhibitors (TNFi; COAST-W). Work productivity was Digital Features To view digital features for this article go to
Journal of Crohn's and Colitis
Background Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). This novel analysis evaluated tofacitinib outcomes using items from the Inflammatory Bowel Disease Questionnaire-32 (IBDQ) and Short Form-36 Health Survey (SF-36) as proxies for key UC patient-reported outcomes (PROs) of fatigue, urgency, abdominal pain and sexual dysfunction over 52 weeks of maintenance treatment. Methods Data from 593 patients with UC in OCTAVE Sustain (NCT01458574) were included.1 PROs were assessed via self-reported proxy items for each UC symptom/dysfunction of interest in the IBDQ and SF-36. A longitudinal mixed-effects model compared tofacitinib 5 and 10 mg twice daily (BID) vs placebo up to 52 weeks for change from baseline (CFB) in each predefined IBDQ and SF-36 item. Least squares (LS) mean differences and standardised effect sizes (ES; LS mean difference divided by the standard deviation [SD] of baseline item scores) were calculated for to...
Clinical Rheumatology, 2015
The objective of the present study is to determine the factors associated with persistent fatigue in patients with severe rheumatoid arthritis (RA) and good disease response to 6 months of tumour necrosis factor inhibitor therapy. Eligible patients with either persistent (PF) or no fatigue (NF) were compared. Using validated questionnaires and bivariate analysis, this cross-sectional survey explored if clinical characteristics, pain, self-efficacy, sleep and mood/depression differed between groups. Patients with PF (PF; NF) (n=28; 28) reported significantly more overall pain (11.3±9.4 (0-33); 6.9±8.9 (0-33)), more recent and current pain intensity (41.4±26.6 (0-80) 24.4±26.6 (0-100) and depression (11.8±7.5 (1-35); 8.2 ±6.6 (0-26)), than the NF group. There was no significant difference between groups in self-efficacy and both groups experienced poor sleep quality (Pittsburgh Sleep Quality Index >5). Despite having good disease response, the PF group had significantly higher rheumatoid factor incidence, disease activity score-28, early morning stiffness duration and lower incidence of ever-failing disease-modifying anti-rheumatic drugs than the NF group. These findings enhance the fatigue literature in patients with RA prescribed tumour necrosis factor (TNF) inhibition therapy, identifying the potentially modifiable factors of pain and depression, previously demonstrated to be strongly associated with fatigue in non-biologic populations. In addition, this study highlights the association between persistent fatigue and an ongoing state of low disease activity. This infers that more judicious disease management could minimise the symptom burden of pain and depression and consequentially fatigue.
Open Access Rheumatology: Research and Reviews, 2012
To determine the impact of tocilizumab on physical function and quality of life in patients diagnosed with rheumatoid arthritis. Methods: A systematic literature review was performed to select for trials that could be used to examine the impact of tocilizumab on patients in terms of health-related physical function, quality of life, and quality of sleep. By examining background therapy, disease duration, and remission rates, we were able to determine the impact that a dose of tocilizumab has on various patients. Results: A total of 2617 tocilizumab-treated patients and 1271 controls were available for this study. Tocilizumab improved the Health Assessment Questionnaire Disability Index score statistically in comparison to the controls, with odds ratios from 1.4 to 7.0. Tocilizumab improved the physical function measure substantially more than the minimal clinically important difference (MCID) (5 units) -8.9 and 9.7 -compared to 4.1 and 5.0 for controls. Seven and nine units of improvement were observed when measuring fatigue in rheumatoid arthritis patients. Using the Epworth Sleepiness Scale, we found that sleep improved (from 7.7 [3.1] to 3.4 [2.2]). Conclusion: Tocilizumab improves function and quality of life and decreases fatigue in patients with rheumatoid arthritis.