Rheumatology and Therapy最新文献

Objective: Gout is a progressive form of arthritis that causes significant pain and disability. Patients with treatment-refractory (or uncontrolled) gout experience a higher prevalence and severity of comorbidities than those whose gout is controlled. Pegloticase is a recombinant PEGylated uricase indicated for the treatment of gout in patients refractory to conventional therapy. We evaluated the treatment journey of patients with chronic uncontrolled gout before initiation of pegloticase therapy.

Methods: Using IQVIA's PharMetrics^® Plus database, we conducted a retrospective observational analysis of adults with ≥ 1 pegloticase claim between April 1, 2011, and August 31, 2020. Demographics were assessed at baseline. Clinical outcomes, health care resource utilization (HCRU), and associated costs were compared over two 12-month periods (months 13-24 and 1-12) prior to the first pegloticase claim (index date).

Results: The study included 408 patients. Prevalence of all gout-associated conditions increased between months 1-12 and 13-24 (P < 0.05 for all). The percentage of patients with tophi increased from 15.4% to 61.5%, the percentage with ≥ 1 flare increased from 49% to 84%, and mean number of flares per patient increased from 1.0 to 2.1 (P < 0.0001 for all). The frequency of all categories of HCRU except emergency department visits also increased (P < 0.0001 for all), as did gout-related healthcare utilization (P£0.005).

Conclusions: Patients with uncontrolled gout experienced an increase in the clinical burden of disease and HCRU in the 2 years before the initiation of pegloticase. Earlier patient identification and initiation of potentially effective therapy may help alleviate these burdens.

Introduction: Inflammatory bowel disease (IBD) related arthritis is the most prevalent extraintestinal manifestation (EIM) of IBD, ranging between 10 and 39%. Magnetic resonance enterography (MRE) is used to assess small bowel disease involvement in Crohn's disease (CD) and can detect signs of sacroiliitis in up to 23.5% of patients. The predicting role of sacroiliitis detected on MRE is still unknown. The aim of this study is to evaluate the predictive role of sacroiliitis at MRE and other clinical features for IBD-related arthritis development in a cohort of adult patients with CD.

Methods: Between December 2012 and May 2020, consecutive patients with CD who performed MRE were enrolled in the study. Patients with a previous diagnosis of IBD-related arthritis were excluded. A baseline demographics and clinical characteristics of the patients were retrospectively collected. The identification of new-onset IBD-related arthritis events during the follow-up was based on rheumatological clinical diagnosis and fulfillment of the ASAS classification criteria.

Results: Ninety-five patients, mean age 43.9 years (standard deviation [SD] ± 16.6), 52.6% female were enrolled in the study with a median follow-up of 83 months (Q25:75 25:143). Six out 95 (6.3%) developed IBD-related arthritis with a mean time of 11 months (SD ± 16.8). Sacroiliitis detected on MRE was not associated with an increased risk of IBD-related arthritis (odds ratio [OR] = 2.12 [95% confidence interval (CI) 0.36, 12.53, p = 0.408]). In contrast, the presence of arthralgia and EIMs were found to be a predictor for IBD-related arthritis development (OR = 84.0 [95% CI 8.18, 862.39, p < 0.0001] and OR = 7.37 [95% CI 1.25, 43.32, p = 0.027], respectively).

Conclusions: This study highlights that sacroiliitis, as assessed by MRE, was not associated with the development of IBD-related arthritis, whereas extraintestinal manifestations and arthralgia were significantly associated with later IBD-related arthritis development in patients with CD.

Introduction: We aim to assess the association of patient-reported pain and remission or low disease activity (LDA) at 3 months (M) in patients receiving baricitinib or other treatments in RA-BE-REAL.

Methods: RA-BE-REAL reports on patients with rheumatoid arthritis (RA) who were prescribed, for the first time, baricitinib (cohort A) or a tumour necrosis factor inhibitor (TNFi) (cohort B-TNFi) or any other mode of action (OMA) (cohort B-OMA). Pain was measured using the visual analogue scale (VAS) (0-100 mm) and clinically meaningful pain improvement thresholds of ≥ 30%, ≥ 50% and ≥ 70% from baseline to 3, 6, 12 and 24 M.

Results: At 3 M, the mean change from baseline (CFB) pain VAS of patients in remission/LDA was - 32.6 mm (cohort A), - 27.3 mm (cohort B-TNFi) and - 28.0 mm (cohort B-OMA). Almost half the patients who were in remission/LDA receiving baricitinib achieved ≥ 70% pain relief. At 3 M, the proportion of patients in remission/LDA with pain VAS ≤ 20 mm was 62.1% (cohort A), 55.0% (cohort B-TNFi) and 55.6% (cohort B-OMA), while for those not in remission/LDA, it was 8.5% and 8.7% (cohort A and B-TNFi, respectively) and 5.3% (B-OMA). More patients on baricitinib achieved pain improvement in all analyzed thresholds than patients in cohort B-TNFi and B-OMA at 3 M. At 24 M, - 26.2 mm (cohort A), - 20.8 mm (cohort B-TNFi) and - 16.0 mm (cohort B-OMA) mean CFBs in pain measurement were observed. For baricitinib and the other treatments, residual pain decreased with achievement of remission/LDA and was sustained up to 24 M.

Conclusions: Patients in remission/LDA receiving baricitinib are more likely to achieve pain control than patients receiving TNFi/OMA.

Introduction: While modern treatments can prevent progressive bone destruction in patients with rheumatoid arthritis (RA) achieving clinical remission, it is unclear whether residual clinical activity may cause or be associated with progressive joint damage. This post hoc analysis evaluated the association between clinical disease activity and structural progression in patients with RA treated with filgotinib (FIL) in FINCH 1 (NCT02889796).

Methods: Patients with RA and inadequate response to methotrexate (MTX) use were randomized 3:3:2:3 to FIL 200 mg (FIL200) or FIL 100 mg (FIL100) once daily, adalimumab 40 mg biweekly, or placebo, all with background MTX. We evaluated the change from baseline (CFB) in modified total Sharp score (mTSS), erosion score, and joint space narrowing score among patients achieving Clinical Disease Activity Index (CDAI) remission (CDAI ≤ 2.8), low disease activity (LDA; 2.8 < CDAI ≤ 10), medium disease activity (MDA; 10 < CDAI ≤ 22), and high disease activity (HDA; CDAI > 22) at 24 weeks.

Results: At week 24, the least squares (LS) mean CFB in mTSS was similarly low across treatments among patients who achieved CDAI remission (range 0.00-0.11) or LDA (n = 285 and 575, respectively). In patients with MDA and HDA (n = 471 and 157, respectively), smaller LS mean CFB in mTSS was seen in the FIL200 group vs. the placebo group (P < 0.05 for both).

Conclusions: RA clinical remission and LDA achievement were associated with suppressed progression of joint destruction over 24 weeks in all treatment groups. Only FIL200 significantly inhibited joint damage compared with placebo in patients with MDA or HDA, indicating an uncoupling of clinical disease activity and structural progression in patients receiving FIL200.

Trial registration: NCT02889796.

The transition from a comorbidity-based to a multimorbidity-focused to ultimately a network medicine approach in people with rheumatic diseases might mark a significant shift in how we understand and manage these complex conditions. Multimorbidity expands on the concept of comorbidity by encompassing the presence of multiple diseases, which results in further individual and societal impacts. This approach, while valuable, often leads to fragmented care focused on individual diseases rather than the patient as a whole.Network medicine, on the other hand, offers a more integrated perspective. It is an emerging concept that leverages the understanding of biologic networks and their interactions within the human body to gain insights into disease mechanisms. In the context of rheumatic diseases, network medicine involves examining how different diseases interconnect and influence each other through shared pathways, genetic factors, and molecular mechanisms.This paradigm shift allows for a more holistic understanding in how we manage rheumatic diseases. For instance, rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus are not just a collection of symptoms affecting various organs but are also interconnected through underlying systemic inflammatory processes, immune system dysregulation, and genetic predispositions.

Current literature regarding cancer risk in rheumatic and musculoskeletal diseases (RMDs) is particularly poor and controversial, even though the incidence of malignancy in some patients with RMDs is considered to be increased compared with the general population. Malignancy may be a major comorbidity in subjects with spondyloarthritis (SpA) as the result of multifactorial mechanisms, from disease pathogenesis to the iatrogenic effect of immunomodulating drugs. Several recommendations for screening and management of cancer risk have been developed in recent years with the aim of improving the different outcomes in these patients. The goal of this narrative review is to provide an overview of the currently available evidence on the risk of malignancy connected with RMDs and examine the association of SpA with cancer and the potential impact of its treatment with biologic and targeted synthetic disease-modifying anti-rheumatic drugs on development of malignancy.

Introduction: Lorecivivint (LOR), a CDC-like kinase/dual-specificity tyrosine kinase (CLK/DYRK) inhibitor thought to modulate inflammatory and Wnt pathways, is being developed as a potential intra-articular knee osteoarthritis (OA) treatment. The objective of this trial was to evaluate long-term safety of LOR within an observational extension of two phase 2 trials.

Methods: This 60-month, observational extension study (NCT02951026) of a 12-month phase 2a trial (NCT02536833) and 6-month phase 2b trial (NCT03122860) was administratively closed after 36 months as data inferences became limited. Participants received a single intra-articular LOR or placebo (PBO) injection at their parent-trial baseline. The primary outcome was the comparative incidence of serious adverse events (SAEs), with AEs and similar safety measures comprising secondary outcomes. A post hoc baseline-adjusted analysis of covariance (ANCOVA) compared changes from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Function subscores and medial joint space width (JSW) between LOR 0.07 mg and PBO groups in a subpopulation of participants with unilateral knee pain and widespread pain low enough to allow participants to differentiate their target knee pain.

Results: The safety analysis set for the extension study included 495 LOR-treated and 208 control participants, with 409 (82.6%) and 175 (84.1%) remaining at study close, respectively. There were 68 SAEs reported in 38 (5.4%) patients; none were considered treatment-related by investigators. The incidence of AEs was similar between groups. In the post hoc subgroup efficacy analyses, LOR 0.07 mg demonstrated greater mean improvements from baseline compared with PBO in WOMAC pain and function scores out to 12 months post-injection. No between-group differences in medial JSW were observed out to 18 months.

Conclusions: LOR appeared generally safe and well tolerated. Efficacy analyses on the subset of completer patients demonstrated durable symptom improvements in WOMAC pain and function for at least 12 months compared to PBO after a single injection of LOR.

Clinical trial registration number: NCT02951026.

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophil-associated disease (EAD) characterized by inflammation in small- to medium-sized blood vessels. In the REal-world inVestigation of Eosinophilic-Associated disease overLap (REVEAL) study, overlap among 11 EADs was assessed. In the present sub-study, we evaluated EGPA overlap with other EADs, all-cause EAD- and EGPA-related healthcare resource utilization (HCRU) and costs, and their relationship with blood eosinophil count and treatments received.

Methods: REVEAL, a retrospective study, used Optum's de-identified Clinformatics^® Data Mart Database. In this sub-study, eligibility criteria included an age of ≥ 12 years, ≥ 1 EAD, continuous health-plan eligibility, and compliance with the EGPA/GPA case definition per International Classification of Diseases Ninth/Tenth Revision diagnostic codes between 1 January 2015 and 30 June 2018. Patients were grouped based on whether they had received immunomodulators/cyclophosphamide/mepolizumab (ICM) or not (non-ICM).

Results: Of 701 patients with EGPA, 29.5% were in the ICM group. Overall, 72.2% had ≥ 1 overlapping EAD. The number of overlaps was similar for the ICM and non-ICM groups. In patients with blood eosinophil counts ≥ 300 cells/µL, 22.8% had ≥ 1 overlapping EAD. The mean annual all-cause cost was $98,644, 54.1% of which was from outpatients and 33.6% from inpatients. The mean annual EAD- and EGPA-related costs were $23,820 and $9,306, respectively. Patients in the non-ICM group versus the ICM group had higher all-cause ($101,560 vs $91,684) but lower EAD-related ($22,733 vs $26,412) and EGPA-related ($6,171 vs $16,786) costs. All-cause HCRU and costs increased with increasing overlap.

Conclusions: EGPA was associated with substantial HCRU and costs, driven by outpatient and inpatient settings. More overlapping EADs were associated with higher HCRU and costs, highlighting the need for treatment to reduce healthcare expenditure in these patients. Infographic available for this article.

Introduction: To conduct a literature review exploring the humanistic burden, costs, and guideline recommendations for non-surgical management of moderate-severe pain in knee osteoarthritis (KOA).

Methods: Published studies (2018-25 April 2023) assessing the burden of moderate-severe pain in KOA were identified by searching Medline, Embase, EconLit, and Cochrane database, supplemented with grey literature hand searches and reference list snowballing. Treatment guidelines were also identified for key countries.

Results: This review included 106 publications and 37 treatment guidelines. Patients with moderate-severe pain were found to experience a low quality of life (QoL) and an impaired ability to perform daily tasks. The economic burden of KOA was substantial, including cost of medical visits, non-operative treatment (physical therapy and hyaluronic acid [HA] being key drivers) and productivity losses. Non-steroidal anti-inflammatory drugs (NSAIDs) were among the most frequently used pharmacological treatments, with intra-articular (IA) injections used to varying degrees. Opioid use was also frequently reported. Guidelines universally recommended NSAIDs, albeit with limited dose and duration for oral NSAIDs. IA-corticosteroids were conditionally/moderately recommended for short-term use by most guidelines, while IA-HA and opioids were rarely recommended. Guidelines are not specific to patients with moderate-severe pain and do not distinguish between different KOA phenotypes.

Conclusions: KOA with moderate-severe pain is associated with substantial humanistic and economic burden. Real-world data suggest that some treatments are regularly used at high cost regardless of the lack of evidence-based recommendations. There remains a need for new treatment options that successfully relieve pain, improve QoL and delay the need for surgery. Graphical abstract available for this article.

This commentary explores the potential cardiovascular (CV) benefits of combining methotrexate (MTX) and Janus kinase inhibitors (JAKis) in the treatment of rheumatoid arthritis (RA). While European guidelines recommend MTX as first-line treatment, concerns about the CV risks associated with JAKis have emerged. This article reviews the existing literature to assess the role of concomitant MTX in reducing CV risk when used with JAKis. Clinical trials confirm the efficacy of JAKis in combination with MTX in terms of treatment outcomes in RA. However, the number of major adverse cardiovascular events (MACEs) reported is too low to draw conclusions on adverse CV outcomes. Indirect evidence does, however, suggest potential protective effects of MTX on CV outcomes, as several mechanisms may contribute to MTX's cardioprotective effects, including reduced inflammation, adenosine monophosphate-activated protein kinase (AMPK) activation, increased cholesterol efflux, and adenosine accumulation. These mechanisms and the available data may support the case for CV benefits of concomitant MTX when JAKis are used in the treatment of patients with RA, although further research is needed. In particular, the lipid paradox associated with RA highlights the complex relationship between RA treatments (MTX, JAKis, tumor necrosis factor (TNF) inhibitors, and interleukin (IL)-6 receptor inhibitors), inflammation, different lipid profiles, and CV risk. In the absence of contraindications and when MTX is tolerated, this commentary suggests the concomitant use of MTX and JAKis as a preferred option for optimizing CV protection in patients with RA.