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

Hyperbaric oxygen therapy (HBOT) may have positive effects on pain, fatigue, multidimensional function, sleep disturbance, tender points, and patient global in patients with fibromyalgia (FM), according to a study published in 

 Low pressure (less than 2.0 atmospheric absolute) may be able to reduce adverse events. However, future studies are needed to determine optimal protocols.

“Accumulating evidence suggests that HBOT is a non-invasive modality with lasting efficacy to treat FM,” lead investigator Xinxin Chen, MD, of the Rehabilitation Medical Center at West China Hospital, Sichuan University, China, and colleagues, stated. “HBOT is conducted by intermittently breathing 100% oxygen in a pressure chamber above one atmospheric absolute pressure (ATA). HBOT can raise the partial pressure of oxygen in alveoli, leading to a favorable increase in dissolved oxygen in plasma.”

PubMed, EMBASE, Web of Science, Cochrane Library, Wan Fang, China National Knowledge Infrastructure (CNKI), and the China Science and Technology Journal Database (VIP) were used in the systematic review and meta-analysis to determine the safety and efficacy of HBOT for the treatment of FM.

Databases were searched from inception through October 2022 to identify relevant clinical trials, both randomized controlled (RCT) and non-randomized controlled (non-RCT). Once recognized, 2 researchers screened the data and evaluated the study quality. The risk of bias was determined via the Cochrane Collaboration checklists and the Methodological Index for Non-randomized Studies, while meta-analysis was conducted by RevMan V.5.4.1 software.

The primary outcome measure was pain, while secondary outcomes included patient global, sleep disturbances, fatigue, tenderness, multidimensional function, and any adverse events.

Ultimately, 9 studies (3 RCTs and 6 non-RCTs), comprised of 288 patients, were included in the review. Pain assessment was evaluated using results from the Visual Analogue Scale (VAS) and Widespread Pain Index (WPI). HBOT was able to better alleviate pain in this patient population when compared with the control intervention (standardized mean difference [SD] = −1.56, 95% confidence interval [CI] (−2.18 to –0.93), 

The majority of included studies observed improvements in fatigue, patient global, sleep disturbance, multidimensional function, and tender points. One study assessing patient global reported that at 3-month follow-up, patients stated that their fibromyalgia symptoms were “a great deal better,” indicating that the effects of HBOT may be long-term.

Although no serious adverse events were reported, adverse events occurred in 23.8% (n = 44/185) patients, which led to 6.5% (n = 12) patients withdrawing from the study. The most common adverse events were mild barotrauma, new-onset myopia, headache, dizziness, claustrophobia, and an inability to adjust ear pressure.

The study was limited by the small number of RCTs included, which may have led to an overall risk of bias or insufficient evidence. Further, the HBOT protocols between studies had clinical heterogeneity, which may have skewed results. No subgroup analysis evaluating the efficacy of different regimens could be performed due to these factors. Lastly, only data from Chinese and English databases were included, thus potentially limiting data availability.

“There is growing evidence that HBOT is a non-invasive way to treat chronic pain diseases with long-lasting efficacy and minor adverse effects,” Chen concluded. “In murine models of pain, HBOT has been shown to inhibit pain sensation, which may be due to the nitric oxide-dependent release of opiate peptides and could be restrained by an antagonist, naltrexone.”

Chen X, You J, Ma H, Zhou M, Huang C. Efficacy and safety of hyperbaric oxygen therapy for fibromyalgia: a systematic review and meta-analysis. BMJ Open. 2023;13(1):e062322. Published 2023 Jan 23. doi:10.1136/bmjopen-2022-062322

Articles

The majority of included studies observed improvements in pain, fatigue, patient global, sleep disturbance, multidimensional function, and tender points. 

Hyperbaric Oxygen Therapy may Improve Pain, Fatigue in Patients with Fibromyalgia 

Treatment with anakinra, an interleukin-1 (IL-1) inhibitor, was safe and effective for managing flares in difficult-to-treat patients with gout, according to a study published in 

 Used in multiple complex scenarios, such as polyarticular gout, dialysis, active infections, and chronic kidney disease, the drug was also proven to be effective as a long-term treatment. However, concerns remain regarding certain safety aspects.

“Nonsteroidal anti-inflammatory drugs, corticosteroids, and colchicine are the first-line agents, although they are contraindicated in many patients,” lead investigator, Sicylle Jeria Navarro, MD, of the Rheumatology Department at the Hospital Universitari de la Santa Creu i Sant Pau in Barcelona, Spain, and colleagues, explained. “Blockade of IL-1 with anakinra can be an alternative.”

Information from patients with gout from a tertiary teaching referral center in Barcelona was extracted from medical records between January 2009 and December 2020. Reviewers performed a 2-stage screening process by title/abstract and full-text reading of 1519 citations. Ultimately, 28 articles met inclusion criteria and were used for data extraction and synthesis. Any experience in difficult-to-treat and complex clinical scenarios were described. Comorbidities included chronic kidney disease, transplantation, dyslipidemia, diabetes mellitus, hypertension, and cardiovascular disease.

The sample of 551 patients with gout identified and analyzed 648 flares. The mean age was 57.9 years and most (82.9%) of patients were male. Clinical presentation of gout was classified as 66.9% tophaceous and 47.5% polyarticular and more than half of patients had at least 1 associated comorbidity.

Ten patients treated with anakinra for gout flare were included in the case series, with a median age of 70.5 years and 90% were male. In total, 65 patients in the clinical complex scenarios portion presenting an active infection, 41 transplanted patients, and 14 in hemodialysis received anakinra. The drug did not affect response to prior antimicrobial therapy given before the first anakinra dose in any of these patients.

Anakinra effectively treated flares (93.9%, n = 598) and was successful as a long-term treatment option (91%) and well tolerated, with response to treatment reported as complete or partial within 1-3 days. Only 28 patients (5.1%) were non-responders.

In terms of safety, a total of 6.7% (n = 34) adverse events (AEs) were reported in the flare treatment group, most of which classified as mild or transient, which were more common in those receiving the drug long-term. The most common AEs were injection site reactions, reversible hematological disorders, and acute infections. In patients placed in the long-term treatment category, 7 infections were reported, including 2 staphylococcus aureus tophus infections, an S aureus lung abscess, an erysipelas infection of the leg, a Streptococcus B urinary tract infection, and arthritis of the knee due to S aureus.

The cross-sectional study design and using most of the data included from the case series limited results. Further, investigators were unable to compare studies due to the heterogeneity of flare, refractory gout, or clinical improvement definitions. Lastly, a systematic review or meta-analysis could not be performed.

“The use of anakinra for the treatment of acute gout flares seems to be an effective and safe alternative to the standard of care,” Jeria Navarro concluded. “High-quality control trials are needed for the standardization of the use of anakinra in gout patients, especially for refractory cases.”

Jeria-Navarro S, Gomez-Gomez A, Park HS, et al. Effectiveness and safety of anakinra in gouty arthritis: A case series and review of the literature. Front Med (Lausanne). 2023;9:1089993. Published 2023 Jan 12. doi:10.3389/fmed.2022.1089993

Anakinra effectively treated 94% of the gout flares included in the study sample and was a viable long-term treatment option.

Anakinra Safely, Effectively Manages Difficult-to-Treat Gouty Arthritis 

A real-life study reported low persistence for all biologics at the 3-year mark in patients with psoriatic arthritis (PsA) who were previously exposed to a tumor necrosis factor inhibitor (TNF), according to a study published in 

Results indicated that persistence was higher in patients receiving an interleukin-17 (IL-17) or IL-12/23 when compared with TNF.

“Tumor necrosis factor inhibitor (TNF) agents are most often the first-choice biological treatment for patients with PsA,” lead investigator, Laura Pina-Vegas, MD, of the rheumatology department at the Hôpital Henri Mondor in Creteil, France, stated. “When their discontinuation is needed, a switch to another TNFi or to another therapeutic class may be considered. However, data supporting one approach over another are lacking.”

Adult patients with PsA starting a second-line biological after discontinuing a TNF were enrolled in the nationwide cohort study. Data from the French health insurance system (Système National des Données de Santé [SNDS]), which was linked to the hospital discharge database, were utilized during the study period spanning from January 2015 through December 2020. Data included sociodemographic data, reimbursements for health-related expenditure, outpatient medical care, nursing care, pharmacy-dispensed medications, medical interventions, and information related to admissions to French hospitals.

The primary outcome was persistence of a biologic, both originator and biosimilar. Persistence, defined as the time from biologic initiation to discontinuation (a period of over 60 days without refilling the same prescription), was assessed by the Kaplan-Meier method.

Poisson regression models, divided into 6-month intervals, were used to compare the persistence by biological class. Investigators emphasized the importance of treatment persistence for determining the value of a drug as well as an indicator of patient interest.

In total, 2975 patients started a second-line biologic during the study period, with 53% (n = 1580) initiating a second TNF, 33% (n = 969) starting an IL-17, and 14% (n = 426) initiating an IL-12/23. The mean age was 47 years, 35% were male, and the median follow-up was 229 days. During the follow-up period, 73% (n = 2168) patients discontinued their second-line biologic. At 1-year, 2-year, and 3-year marks, persistence rates were 42%, 25%, and 17%, respectively.

Persistence was linked to treatment with IL-17 or IL-12/23 (adjusted relative risk [RRa] 0.79, 95% confidence interval [CI] 0.71 to 0.87 and RRa 0.69, 95% CI 0.61 to 0.79, respectively) when compared with TNF. There were no significant differences between patients receiving IL-17 and IL-12/23 (RRa 0.88, 95% CI 0.76 to 1.02).

Hospital prescriber information was incomplete. However, sensitivity analysis after excluding these patients reported stable results. Further, while investigators defined drug exposure based on reimbursement data, which may not be equivalent to days of use, adherence rates are typically higher for biologics when compared with other treatment categories. Investigators mitigated potential channeling bias by limiting the analyses to patients receiving a second therapeutic biological sequence after discontinuing a first TNF. Lastly, information collected in the database did not specify why a patient discontinued a biologic.

Despite this, the cohort included a large sample of patients from a national database, which ensures homogenous data processing, thus limiting selection bias.

“This real-life study… highlights that long-term control of PsA most often requires multiple therapeutic lines, including molecules with different modes of action,” Pina-Vegas concluded. “Further studies, including head-to-head randomised trials, would be useful to confirm these findings and identify patient subgroups that may benefit from one management strategy over another.”

Pina Vegas L, Hoisnard L, Bastard L, Sbidian E, Claudepierre P. Long-term persistence of second-line biologics in psoriatic arthritis patients with prior TNF inhibitor exposure: a nationwide cohort study from the French health insurance database (SNDS). RMD Open. 2022;8(2):e002681. doi:10.1136/rmdopen-2022-002681

Adult patients with psoriatic arthritis starting a second-line biological after discontinuing a TNF were enrolled in the nationwide cohort study.

Study Shows Low Persistence Rate for Biologics in Previously TNF-Exposed Patients with Psoriatic Arthritis 

A 16-week “Plants for Joints” (PFJ) multidisciplinary lifestyle program significantly improved metabolic status while decreasing disease activity in patients with rheumatoid arthritis (RA) with low-moderate disease activity, according to a randomized controlled study published in 

“Reversing and preventing adverse lifestyle factors could potentially reduce the incidence and burden of RA, as well as alleviate its comorbidities,” investigators hypothesized. “Specifically, beneficial effects have been found in interventions directed at single lifestyle factors, such as dietary interventions with plant-based or Mediterranean diets, physical exercise programs, or stress reduction techniques.”

The PFJ parallel-arm, assessor-blind, randomized controlled trial enrolled patients with RA and Disease Activity Score-28 (DAS28) between ≥2.6 and ≤5.1 were randomized to the PFJ cohort or the control group. The 16-week program was based on previous protocols and guidelines regarding a whole-food, plant-based diet, stress management, and physical activity. Groups of 6 to 12 participants met for 2- to 3-hour meetings for a total of 10 sessions. Although 17 patients had live meetings, 23 patients received the intervention in hybrid form due to COVID-19 restrictions. Patients in the control group received usual care. Stable medication was maintained 3 months before and during the trial, when possible. 

Investigators hypothesized that the PFJ program would lower disease activity, which was defined as the primary outcome. Other outcomes including patient-reported, metabolic, and anthropometric measurements. The differences between groups were evaluated through intention-to-treat analysis with a linear mixed model adjusted for baseline values.

In total, 77 patients completed the study (mean age of 55 years, 92% female, mean DAS28 of 3.8 [0.7], and a body mass index [BMI] of 26 [4] kg/m

). At the 16-week mark, the PFJ cohort had a mean 0.9-point greater improvement of DAS28 (95% CI 0.41, 1.29; 

0.0001) when compared with the controls. The intervention also led to greater decreases in low-density lipoprotein (–0.32 mmol/l), Hemoglobin A1C (HbA1c; -1.3 mmol/mol), fat mass (-2.8 kg), waist circumference (-3 cm), and body weight (difference -3.9 kg) when compared with controls. However, blood pressure, glucose, other lipids, and patient-reported outcome measures did not change during the intervention period.

The low drop-out rate, coupled with the ability to demonstrate substantial effects despite low disease activity, strengthened the study. Further, findings highlight the health benefits of a plant-based diet, emphasizing the advantages of this type of diet as a part of a more sustainable lifestyle. However, the intervention group received extra attention, which may have partially attributed to improvement in subjected measures. Lastly, participants may have been more interested in lifestyle changes instead of medication when compared with average patients with RA. However, investigators stress that this factor should not lessen the potential of this intervention protocol.

A 2-year extension evaluating cost effectiveness, critical nutrients, disease-modifying antirheumatic drug (DMARD)-tapering protocol, bone mineral density, and body composition will be offered to all participants in the control group. Future studies are needed to determine whether plant-based diet can mirror the anabolic effect of animal-based proteins.

“The program is readily compatible with drug therapy and could potentially lower the need for medication for both RA as well as for metabolic syndrome–related conditions,” investigators concluded.

Wendy Walrabenstein, Carlijn A Wagenaar, Marike van der Leeden, Franktien Turkstra, Jos W R Twisk, Maarten Boers, Henriët van Middendorp, Peter J M Weijs, Dirkjan van Schaardenburg, A multidisciplinary lifestyle program for rheumatoid arthritis: the ‘Plants for Joints’ randomized controlled trial, Rheumatology, 2023;, keac693, https://doi.org/10.1093/rheumatology/keac693

“Reversing and preventing adverse lifestyle factors could potentially reduce the incidence and burden of rheumatoid arthritis, as well as alleviate its comorbidities,” investigators hypothesized. 