Rheumatology and Therapy最新文献

Introduction

This study aimed to develop low-cost models using machine learning approaches predicting the achievement of Clinical Disease Activity Index (CDAI) remission 6 months after initiation of tumor necrosis factor inhibitors (TNFi) as primary biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatoid arthritis (RA).

Methods

Data of patients with RA initiating TNFi as first b/tsDMARD after unsuccessful methotrexate treatment were collected from the FIRST registry (August 2003 to October 2022). Baseline characteristics and 6-month CDAI were collected. The analysis used various machine learning approaches including logistic regression with stepwise variable selection, decision tree, support vector machine, and lasso logistic regression (Lasso), with 48 factors accessible in routine clinical practice for the prediction model. Robustness was ensured by k-fold cross validation.

Results

Among the approaches tested, Lasso showed the advantages in predicting CDAI remission: with a mean area under the curve 0.704, sensitivity 61.7%, and specificity 69.9%. Predicted TNFi responders achieved CDAI remission at an average rate of 53.2%, while only 26.4% of predicted TNFi non-responders achieved remission. Encouragingly, the models generated relied solely on patient-reported outcomes and quantitative parameters, excluding subjective physician input.

Conclusions

While external cohort validation is warranted for broader applicability, this study highlights the potential for a low-cost predictive model to predict CDAI remission following TNFi treatment. The approach of the study using only baseline data and 6-month CDAI measures, suggests the feasibility of establishing regional cohorts to generate low-cost models tailored to specific regions or institutions. This may facilitate the application of regional/in-house precision medicine strategies in RA management.

Introduction

The objective of this analysis is to evaluate the improvement in spinal pain with ixekizumab, placebo, and adalimumab based on objective measures of inflammation response in patients with ankylosing spondylitis (AS).

Methods

The COAST-V 52-week, double-blind, placebo-controlled, randomized phase III trial examined the efficacy of ixekizumab in patients with active AS; adalimumab was used as an active reference arm. Treatment effects on reduction in pain were assessed by objective measures of controlled and persisting inflammation (defined by magnetic resonance imaging [MRI], C-reactive protein [CRP], or MRI + CRP status). Pathway analysis was used to analyze treatment effect that was not attributable to reduction in inflammation biomarkers.

Results

In patients with AS, when inflammation was controlled as assessed by MRI, patients treated with ixekizumab experienced a reduction in spinal pain at night (SP-N, numeric rating scale, ixekizumab mean = − 3.9, p < 0.001, adalimumab mean = − 2.6, p < 0.05) compared to placebo (mean = − 1.6) at week 16. When inflammation was controlled as assessed by MRI + CRP, ixekizumab and adalimumab had numerically greater reductions at week 16 in SP-N versus placebo. All ixekizumab groups had further improvements at week 52. When inflammation was persisting as assessed by MRI + CRP, ixekizumab-treated patients had significant reduction in SP-N (mean = − 3.7, p < 0.001) versus placebo (mean = − 1.7), improvement with adalimumab did not reach significance (mean = − 2.6, p = 0.06). In the pathway analysis at week 16, ixekizumab had a greater effect on pain outcomes compared to adalimumab.

Conclusion

This post hoc analysis is supportive of the hypothesis that ixekizumab reduces pain in AS by additional mechanisms other than the reduction of measurable inflammation.

Trial Registration Number

NCT02696785.

Introduction

The aim of this work is to evaluate secukinumab vs. placebo in a challenging-to-treat and smaller US patient subpopulation of the international FUTURE 2–5 studies in patients with psoriatic arthritis (PsA).

Methods

Data were pooled from US patients enrolled in the phase 3 FUTURE 2–5 studies (NCT01752634, NCT01989468, NCT02294227, and NCT02404350). Patients received secukinumab 300 or 150 mg with subcutaneous loading dose, secukinumab 150 mg without subcutaneous loading dose, or placebo. Categorical efficacy and health-related quality-of-life (QoL) outcomes and safety were evaluated at week 16. Subgroup analyses were performed based on tumor necrosis factor inhibitor (TNFi) status and body mass index (BMI). For hypothesis generation, odds ratios (ORs) for American College of Rheumatology (ACR) 20/50/70 and Psoriasis Area and Severity Index (PASI) 75/90/100 responses by treatment were estimated using logistic regression without adjustment for multiple comparisons.

Results

Of 2148 international patients originally randomized, 279 US patients were included in this pooled analysis. Mean BMI was > 30 kg/m² and 55.2% had prior TNFi treatment. ORs for ACR20/50/70 significantly favored patients receiving secukinumab 300 mg and 150 mg with loading dose vs. placebo (P < 0.05), but not those receiving secukinumab 150 mg without loading dose vs. placebo. For PASI75, ORs favored all secukinumab groups over placebo (P < 0.05); for PASI90 and PASI100, only the secukinumab 300-mg group was significantly favored over placebo (P < 0.05).

Conclusions

In this challenging sub-population of US patients with PsA, secukinumab provided rapid improvements in disease activity and QoL. Patients with PsA and active psoriasis might benefit more from secukinumab 300 mg than 150 mg.

Introduction

The concept of severity in a multidomain disease such as psoriatic arthritis (PsA) is still not well defined. The aim of this study was to identify the clinical characteristics of patients with severe peripheral PsA.

Methods

Retrospective analysis of a longitudinal cohort. Demographic and clinical characteristics of patients with PsA were collected at baseline and at last follow-up. We defined the severe population using the modified Composite Psoriatic Disease Activity Index (mCPDAI); which excludes ankylosing spondylitis quality of life scale). Hence, patients with a score of 3 in at least one domain were defined as having severe PsA. Clinical characteristics of patients fulfilling the definition of severe PsA were compared to those non-severe.

Results

We evaluated 177 patients with peripheral PsA (M/F: 98/76). Of these, 64 (36.1%) were identified as severe according to the mCPDAI criteria, at baseline. Eighteen patients (10.1%) at last follow-up still met the definition of severe PsA. At last follow-up visit, severe patients with PsA were only males (18/18, P < 0.01) and have worse outcomes in terms of disease activity, pain, function, and impact of disease. Male sex and the severity of skin involvement at baseline were factors associated with the presence of severe PsA. The agreement between the presence of severe PsA and the absence of minimal disease activity was slight [Cohen’s k: 0.174 (0.084–0.264)].

Conclusions

Our study showed that severe patients with PsA had more disease activity, pain, and impact of disease than non-severe patients. Furthermore, we demonstrated that severity and disease activity are not interchangeable concepts.

Abstract

Introduction: Randomized controlled trials have demonstrated tofacitinib efficacy for psoriatic arthritis (PsA); however, real-world effectiveness data are limited. This real-world analysis assessed baseline demographics/disease characteristics and tofacitinib effectiveness in patients with PsA in the CorEvitas PsA/Spondyloarthritis Registry.

Methods: This study (NCT05195814) included patients with PsA initiating tofacitinib from December 2017-December 2021, as monotherapy or with oral small molecules (methotrexate/leflunomide/sulfasalazine/apremilast), pre-existing use, or initiated concurrently.

Outcomes: mean change from baseline in disease activity/patient-reported outcomes, proportion of patients achieving low disease activity (LDA)/remission at 6 ± 3 months, and discontinuation rates.

Results: Of 222 patients with PsA who initiated tofacitinib (60.8% as monotherapy), 123 patients had 6 ± 3 months of follow-up. At initiation, 59.7% were female, 92.3% were White, mean age was 56.3 years, PsA duration since diagnosis was 8.2 years, and 25.7% were biologic disease-modifying antirheumatic drug (bDMARD)-naïve. Improvements to 6 ± 3 months were observed with tofacitinib for Clinical Disease Activity Index for PsA (cDAPSA), DAPSA, PsA Disease Activity Score (PASDAS), Clinical Disease Activity Index, body surface area (BSA), tender/swollen joint count, patient fatigue, pain, Patient Global Skin Assessment, and Health Assessment Questionnaire-Disability Index. At 6 ± 3 months, 25.0%/7.8% of patients treated with tofacitinib achieved cDAPSA-defined LDA/remission, 18.2% achieved minimal disease activity, 30.8% had PASDAS ≤ 3.2, 42.9%/29.4% had resolved enthesitis/dactylitis, and 22.5% achieved BSA = 0%. Tofacitinib discontinuation occurred in 51.2% of patients (51.6% of monotherapy initiators) at/prior to 6 ± 3 months (27.6%/23.6%), 57.1% of whom switched to tumor necrosis factor/interleukin-17 inhibitors. Reasons for discontinuation were not reported in 85.3%/79.3% of patients who discontinued at/prior to 6 ± 3 months.

Conclusions: This real-world US cohort analysis described patients with PsA newly initiating tofacitinib; most were bDMARD-experienced or receiving monotherapy treatment. In patients who remained on therapy (48.8%), tofacitinib was effective across multiple PsA domains at 6 ± 3 months. Limitations included small patient numbers at follow-up and potential selection bias.

Trial registration: ClinicalTrials.gov identifier, NCT05195814.

Introduction: CHAMOMILE (CHaracteristics and impact of flares on clinicAl and econoMic OutcoMes In patients with systemic Lupus Erythematosus [SLE]) examined how flares in the year of SLE diagnosis impact future disease activity and damage, productivity, healthcare resource utilization (HCRU), and costs in patients with SLE in Germany.

Methods: CHAMOMILE was a retrospective cohort study of adults with an SLE diagnosis in the German Sickness Fund Database from 1 July 2010 to 31 December 2013. Patients were classified according to their greatest flare severity during the baseline year (none, mild, or moderate/severe). The number and severity of flares were assessed annually over 5-8.5 follow-up years, along with SLE organ/system damage, treatments, work disability, and HCRU metrics.

Results: Of 2088 patients (84.6% female; mean age [standard deviation] 51.4 [16.1] years; mean follow-up 6.8 [2.1] years), 34.3% (n = 716) were flare-free, 29.8% (n = 622) had mild flares, and 35.9% (n = 750) had moderate/severe flares at baseline. Baseline flare severity was related to future flares: rates during follow-up were higher in patients with moderate/severe baseline flares compared with those with mild or no baseline flares (89.6 vs 78.5 and 44.2 flares/100 patient years, respectively). Overall, 80.2% (n = 1675) of patients received glucocorticoids at least once during baseline and follow-up. Patients' HCRU was generally greatest in their baseline year. Costs were highest in patients with moderate/severe baseline flares.

Conclusion: Baseline flare severity provided insight into a patient's disease course and the clinical and economic burden of SLE over time, highlighting the ramifications of uncontrolled disease for patients with SLE.