Lana Pine is the editor of HCPLive Rheumatology. She is an experienced editor and technical writer with a demonstrated history of working in the banking and publishing industries. In her free time, she enjoys cooking, yoga, listening to podcasts, and drawing. She can be reached via email at LPine@mjhlifesciences.com.

Lana Pine

The systemic inflammatory response index (SIRI) was an influencing factor of acute gout attack, demonstrating its potential to be used as a new inflammatory marker of disease activity in patients with 

Gouty arthritis is characterized by abrupt swelling, redness, pain, and dysfunction of the affected joint and can lead to chronic inflammation, cartilage damage, bone erosion, and damage to the joint tissues. Although erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are used to determine disease activity, they are complex and offer limited clinical application.

 Therefore, other inflammatory markers to assess disease activity are needed.

“Previous studies have shown that the monocyte to lymphocyte ratio (MLR) and neutrophil to lymphocyte ratio (NLR) are higher in patients with GA than healthy controls and may be a strong predictive marker for a gout attack,” wrote a group of Chinese investigators. “However, systemic immune-inflammatory index (SII) and SIRI have never been investigated in patients with gouty arthritis.”

To explore the link between SIRI, SII, and disease activity in gout, investigators conducted a retrospective study at the Affiliated Hospital of North Sichuan Medical College, in China, from March 2018 to May 2023. A total of 873 male patients with primary gout were enrolled in the study: 474 patients with acute gouty arthritis and 399 patients with intercritical gouty arthritis. The study also included 194 age-matched healthy controls. Patients were categorized by whether they presented with a gout flare or not.

Differences in SII, SIRI, platelet to lymphocyte ratio (PLR), NLR, and MLR levels were evaluated. Changes prior to and during treatment in both gout cohorts were assessed. Influencing factors for acute gout flare were determined using multivariate logistic regression and demographic information including age, sex, and body mass index was collected.

Compared with the intercritical gouty arthritis cohort, the PLR, C-reactive protein (CRP), incidence of hyperlipidemia, and the erythrocyte sedimentation rate (ESR) were significantly higher in the acute gouty arthritis. However, the duration of their disease was significantly shorter (

The SII, SIRI, NLR, and MLR levels were significantly higher in the acute gouty arthritis cohort compared with the intercritical cohort and controls (

<.05). After treatment, decreases in SII, SIRI, NLR, and MLR were reported in the acute gout group (

>.05), although no significant differences were observed in the intercritical gout group pre- and post-treatment (

SIRI, SII, MLR, NLR, and PLR were positively associated with ESR and CRP, important inflammatory indicators for measuring disease activity (

<.05). Results of the multivariate logistic regression analysis demonstrated the duration of disease, SIRI, ESR, CRP, and hyperlipidemia were influencing factors of acute gout flare (

<.05). The area under the curve (AUC) of ESR, SIRI, and CRP on the diagnosis in acute gouty arthritis were .664 (95% confidence interval [CI]: .628 – .699), .674 (95% CI: .639 – .709), and .755 (95% CI: .724 – .787), respectively. When diagnosing acute gout, SIRI was superior compared with ESR.

Investigators noted the modest sample size and enrolling all patients from a single center as limitations. They recommend future research focus on multicenter trials with larger sample sizes to confirm the findings.

“This study is the first to evaluate the association between gouty arthritis and SIRI, and the obtained results suggest that the SIRI can serve as a new index capable of assessing disease activity,” investigators concluded.

Jiang Y, Tu X, Liao X, et al. New Inflammatory Marker Associated with Disease Activity in Gouty Arthritis: The Systemic Inflammatory Response Index. 

. 2023;16:5565-5573. Published 2023 Nov 24. doi:10.2147/JIR.S432898

Singh JA, Gaffo A. Gout epidemiology and comorbidities. 

. 2020;50(3S):S11–S16. doi:10.1016/j.semarthrit.2020.04.008

Articles

SIRI emerged as a significant factor influencing acute gout attacks, shedding light on a prospective diagnostic tool.

Study Evaluates SIRI as a Potential Inflammatory Marker in Gouty Arthritis

Juliana Reed, MS: Biosimilars

 is pivotal—it is all about fostering pre-market competition and reducing costs associated with biologic medications. In an interview with 

, Juliana Reed, MS, executive director of the Biosimilars Forum, explained the pivotal role biosimilars play in healthcare, as well as the barriers to access and adoption.

Clinically, Reed said, the most significant aspect is there are currently 8 adalimumab (HUMIRA) biosimilars available. However, these biosimilars face obstacles in reaching the market and achieving uptake. Unfortunately, she explained, pharmacy benefit managers (PBMs) are impeding access to these adalimumab biosimilars, which hinders the potential cost savings and competition these biosimilars could deliver.

“It’s a very expensive medicine, [and if patients] had access to the adalimumab biosimilars they could be saving 85%,” Reed said. “So, that is a significant clinical problem because not being able to have your medicine and save money at the same time creates fiscal hardship on the patients and their families who have to pay these high costs.”

Reed emphasized each of the 8 adalimumab biosimilars costs at least $300 million to develop and takes close to 9 years to reach the market. The developers commit substantial resources to bring cost-effective alternatives to the market, but when access is blocked, it raises concerns about the sustainability of this business model.

Although Reed has witnessed promising progress on Capitol Hill in scrutinizing PBM practices, she would like to see the Centers for Medicare & Medicaid Services (CMS) step up and increase biosimilar uptake. Medicare currently has the lowest adoption rate of biosimilars, and she hopes to see policies favoring higher uptake to attain cost savings.

“We're excited for the future, but we encourage the PBMs to do more to lower costs for patients,” Reed concluded. “It is not about rebates, it is about competition.”

Videos

In an interview with HCPLive, Juliana Reed, MS, explains the pivotal role biosimilars play in healthcare and the barriers to access and adoption.

Juliana Reed, MS: The Crucial Role of Biosimilars in Encouraging Competition, Lowering Costs

 month in review highlights top data demonstrating the efficacy of 2 new adalimumab biosimilars for the treatment of 

 management, and trends in the adoption of biosimilars among patients and clinicians in the United States.

New Adalimumab Biosimilars Show Promise in Inflammatory Bowel Disease

Tumor necrosis factor-α (TNFα) biologics, such as adalimumab, have been widely used to treat inflammatory conditions, including ulcerative colitis (UC) and Crohn’s disease (CD), in Europe and the US. However, the efficacy of the Chinese adalimumab biosimilar, HS016, had not been proven. Similarly, investigators sought to determine whether GP2017 has the same efficacy and safety of reference adalimumab, both in patients naïve to the originator and in patients who switched from the biologic or other adalimumab biosimilars.

Adalimumab Biosimilar HS016 Demonstrates Efficacy, Safety in IBD

Among patients with active CD, most achieved clinical response at weeks 12, 26, and 52 (75.4%, 73.8%, and 50.8%, respectively). Clinical remission was demonstrated in 55.7% at week 12, 65.6% at week 26, and 45.9% at week 52. In the active UC cohort, 37.5% and 50% achieved clinical response at weeks 12 and 26, respectively.

“As research continues, we are confident that increasing biological agents will appear for IBD therapy,” wrote investigators. “Additionally, biosimilars will stimulate competition in the market and have incredible potential to expand patient exposure to biologics in the context of treatment recommendations. Appropriate use of therapeutic drug monitoring (TDM) will provide physicians with a more significant basis for selecting and optimizing treatment.”

Strong Results Observed for Adalimumab Biosimilar GP2017 for Inflammatory Bowel Disease

The research team used a retrospective, multicenter and observational design, conducting their research in Northern Italy at 2 IBD centers: Rho Hospital, ASST Rhodense, and Turin Hospital, Città della Salute e della Scienza, Italy. They involved subjects who had diagnoses of CD or UC who had been given GP2017 therapy for 6 months minimum.

Of the 29 individuals who had begun GP2017 therapy as their first adalimumab, the investigators reported 58.6% were shown to have clinical remission. For the 33 subjects who had had GP2017 as an originator or the 10 who switched from other biosimilars, the investigators found clinical remission was shown to be maintained for 78.8% and 70%, respectively.

The Potential Benefits of Biosimilars in Plaque Psoriasis

This month, results from 2 phase 3 trials evaluating biosimilars for the treatment of plaque psoriasis were announced, including a switch to an adalimumab biosimilar (BI 695501) and a trial assessing the safety and efficacy of the ustekinumab biosimilar, CT-P43.

Switching with Adalimumab Biosimilar Maintains Benefit for Plaque Psoriasis

Research from the phase 3 VOLTAIRE-X trial showed switching from adalimumab reference product to BI 695501 was associated with similar clinical outcomes as maintaining the reference product for patients with chronic plaque psoriasis through 48 weeks. The findings support the prior US Food and Drug Administration (FDA) distinction in approval for the biosimilar last year, when the agency defined BI 695501 as the first “interchangeable” monoclonal biosimilar to adalimumab reference product.

“Based on extrapolation of indications, these results provide rheumatologists, dermatologists, and gastroenterologists with data to support the substitution of BI 695501 for adalimumab reference product in patients with any of the 7 indications for which BI 695501 is approved,” investigators wrote.

CT-P43 Shows Equivalent Efficacy, Safety for Plaque Psoriasis vs Ustekinumab

In the current study, investigators sought to examine the efficacy and safety of CT-P43, a candidate biosimilar, to reference ustekinumab for the treatment of moderate to severe plaque psoriasis.

Results of the phase 3 trial, which included more than 500 patients, provided evidence of equivalent efficacy to originator ustekinumab, with comparable pharmacokinetic, safety, and immunogenicity profiles, in the management of moderate to severe plaque psoriasis in adult patients.

As switching to a biosimilar has become increasingly more common, investigators analyzed data including the switchback rates among a sample of veterans receiving a biosimilar, how a nationwide switch to an adalimumab biosimilar impacted clinicians, and the uptick in trastuzumab biosimilar adoption in the US.

Switchback from Biosimilar to Biologic Rare Among Veteran Patients

In new data from an abstract presented at the International Conference on Pharmacoepidemiology and Therapeutic Risk Management (ICPE) Annual Meeting this year, a team of US-based investigators reported data inconclusive to the notion Veteran patients would primarily switch from a biosimilar product back to its reference biologic product due to a lack of efficacy or safety with the cost-efficient option.

Switching back from a biosimilar to its reference biologic product was not only rare among a cohort of Veterans Affairs patients, but investigators observed there were no distinct trends of rationale as to why a patient would switch back.

Nationwide Switch to Adalimumab Biosimilar Led to Greater Workload, Decreased Satisfaction

Investigators from New Zealand designed an online survey to determine the effect of a mandatory switch to an adalimumab biosimilar. The survey was sent to practicing healthcare professionals including rheumatologists, pharmacists, and nurses specializing in rheumatology.

Overall, the research team reported the switch to the biosimilar, as evaluated by a mean satisfaction score from a scale of 0-10, led to an average rating of about 5.7. The team found providers reported the lowest levels of satisfaction with training involving the biosimilar device, with the information provided from government agencies, and with the administrative work necessary at the time of the transition.

Investigators concluded levels of provider satisfaction were shown to have decreased for elements such as the biosimilar’s safety, its efficacy, the quality of the device, and the availability of alcohol wipes, sharps bins, and support for patients following the change.

Trastuzumab Biosimilar Use Significantly Increasing in the US

An analysis of the utilization of various biosimilars to reference trastuzumab product conducted by a team of US-based academic and industry investigators showed cost-efficient alternatives to the HER2 inhibitor biologic have been increasingly prescribed to patients with relevant cancers since their FDA authorizations 6 years ago

The proportion of total incident episodes using originator trastuzumab biologic decreased from 90% in the pre-biosimilar approval era of 2016, to just 19% in 2021, while biosimilar utilization increased. Additionally, trastuzumab-anns (Kanjinti) increased to 28% use in 2021—a rate similar across patients with and without metastatic disease.

The biosimilars month in review highlights top data demonstrating the efficacy of biosimilars for treating inflammatory bowel disease and plaque psoriasis, as well as trends in adopting biosimilars among patients and clinicians in the US. 

Biosimilars Month in Review: November 2023

Temporomandibular disorders (TMDs) frequently coexist with 

 and chronic widespread pain (CWP), particularly for those with painful myogenous TMDs, according to research published in 

Journal of Oral and Facial Pain and Headache

Fibromyalgia, a chronic condition considered a subgroup of CWP, is characterized by widespread musculoskeletal pain. Concomitant TMD and fibromyalgia is often regarded as a pair of chronic overlapping pain conditions (COPCs). Other COPCs include migraine, chronic tension-type headache, chronic lower back pain, chronic fatigue syndrome, and irritable bowel syndrome (IBS). The similarities between these conditions indicate they are related by epidemiology, symptomology, and underlying mechanisms.

“Although several studies have considered the coexistence of fibromyalgia and TMDs, the association between these 2 disorders remains unexplicit,” wrote lead investigator Pankaew Yakkaphan, DDS, associated with the Faculty of Dentistry, Oral and Craniofacial Science, King's College London, United Kingdom, and colleagues. “Understanding the epidemiologic perspective of this association is instrumental to appropriately diagnosing and managing patients with these conditions.”

A systematic search was conducted among electronic databases, including PubMed, Scopus, Web of Science, MEDLINE, and PsycINFO, to determine the prevalence of CWP and fibromyalgia in patients with TMD, as well as the prevalence of TMDs in patients with fibromyalgia. Study quality was determined using the Newcastle-Ottawa Scale and pooled prevalence estimates were assessed using meta-analyses with defined diagnostic criteria.

A total of 19 moderate to high quality studies were included in the assessment, of which 9 evaluated the prevalence of CWP/fibromyalgia in patients with TMDs and 10 evaluated the prevalence of TMDs in patients with CWP/fibromyalgia. Most (n = 10) studies were case-control, 6 were cross-sectional, and 3 were cohort studies. Heterogeneity of the pooled studies was observed due to varying criteria guidelines and protocols, the subjectivity of patient and clinician assessment, and differences in application over time.

According to the meta-analyses, 3 out of 4 patients with fibromyalgia had concomitant TMDs (76.8% [69.5% - 83.3%]) and approximately one third (32.7%, 4.5% - 71.0%) of patients with TMDs had comorbid fibromyalgia. Compared with disc displacement disorders, myogenous TMDs were more prevalent in this patient population (63.1% [47.7% - 77.3%] vs 24.2% [19.4% - 39.5%], respectively). Comorbid inflammatory degenerative TMDs were observed in 41.8% (21.9% - 63.2%) of patients with fibromyalgia.

The highest proportions of patients with TMDs experiencing fibromyalgia symptoms were observed in a study of patients with painful disorders of the masticatory muscles lasting ≥6 months (63.2%), as well as a study in which patients were referred to a physiatrist to evaluate possible fibromyalgia (52.4%).

Estimates of comorbid CWP in patients with TMDs ranged from 30% to 76%, due in part to classification criteria variances.

As such, investigators noted the potential disparity in prevalence rates due to the differing diagnostic criteria as a limitation of their study. Additionally, although most patients (80% - 90%) were female, which is representative of fibromyalgia, results may not be generalizable to male patients with fibromyalgia and/or CWP. Further hindering generalizability, investigators mentioned most TMD samples were from patients with more severe TMDs who sought treatment. As TMDs are a collective condition, results may not reflect the larger patient population. Lastly, since the review was performed in 2020, there have been additional studies evaluating comorbid TMDs and fibromyalgia/CWP. However, newer findings reinforced the results from this analysis.

“These findings suggest a need for clinicians to consider the overlap between TMDs and CWP/fibromyalgia when treating affected populations, and, where appropriate, to consider multidisciplinary approaches to care,” investigators concluded.

Yakkaphan P, Smith JG, Chana P, et al. Temporomandibular Disorders and Fibromyalgia Prevalence: A Systematic Review and Meta-Analysis. 

. 2023;37(3):177-193. doi:10.11607/ofph.3260

Maixner W, Fillingim RB , Williams DA, Smith SB, Slade GD. Overlapping chronic pain conditions: Implications for diagnosis and classification. J Pain 2016;17(9 suppl):T93- T107.

Approximately one third of patients with temporomandibular disorders had comorbid fibromyalgia.