VIENNA — An intervention consisting of a plant-based diet, exercise, and sleep and stress advice improved pain, stiffness, and physical function in people with knee and/or hip osteoarthritis (OA) and metabolic syndrome, while in patients with rheumatoid arthritis (RA), disease activity improved significantly, and medication use was reduced.
At the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, Carlijn Wagenaar, MD, a PhD candidate in Clinical Immunology and Rheumatology at Amsterdam University Medical Center, Amsterdam, the Netherlands, presented 2-year extension study results for OA and RA and an overview of the possible biological mechanisms underpinning the plant-based intervention in RA.
“At 2 years, RA patients on the PFJ [Plants for Joints] intervention resulted in a significant improvement in disease activity of RA, and these outcomes were maintained 2 years after program end,” Wagenaar reported.
“Some initial improvements in body composition and metabolic outcomes were also maintained at the end of the 2-year extension phase, and there was a net decrease in antirheumatic medication use,” she continued.
In the patients with OA, Wagenaar said the PFJ intervention improved pain, stiffness, and physical function in people with knee and/or hip OA and metabolic syndrome. “In the 2-year extension study, these effects were maintained, and we saw lasting body composition changes and a decrease in cholesterol-lowering medications. There was also high acceptability of the program; the study shows long-term maintenance of clinically relevant effects.”
Intervention Led to Significant Improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Score
In the OA randomized controlled trial, 64 people with hip and/or knee OA and metabolic syndrome were randomized to the PFJ intervention or usual care (waitlist control group). A total of 62 participants (including those in the control group previously) entered the long-term effectiveness study, and 44 had 2 years of follow-up data for analysis. Twenty participants dropped out, with most being unreachable or too busy.
“The PFJ program is a theoretical and practical program where people learn about and follow a whole food, plant-based diet, and receive advice on sleep and stress management and exercise,” said Wagenaar.
The program lasted 16 weeks with group sessions of 6-12 participants. The diet was a plant-based version of the Dutch dietary guidelines with a focus on unprocessed food. It was rich in whole grains, legumes, nuts, seeds, fruit, and vegetables, but without calorie restrictions and participants had one-to-one contact with a dietitian. The exercise advice followed the Dutch exercise guidelines, which advise 150 minutes of moderate to intense exercise per week, as well as twice-weekly muscle strength exercises, noted Wagenaar.
The 2-year follow-up study involved twice-yearly visits and six adherence-promoting webinars per year, as well as monthly newsletters. Researchers also monitored changes in medication intensity (classified as “increased,” “stable,” or “decreased/stopped”) between the start of the PFJ intervention and end of the 2-year extension study, and they were grouped into medications for pain, blood pressure, glucose, and cholesterol.
Participants were encouraged to try and avoid making changes to medication during the intervention phase, but they could do so during the 2-year extension study, said Wagenaar. In fact, the researchers actively monitored and quantified medication changes between the start of the PFJ intervention and end of the 2-year follow-up period.
Patients in the 16-week trial had an average age of 64 years, 84% were women, and their mean body mass index (BMI) was 33 kg/m2. A total of 73% had knee OA and 78% hip OA, and their mean WOMAC score was 38.2, indicative of moderate to severe OA.
In participants who completed the 2-year extension study, the primary outcome (WOMAC score for mean stiffness and physical function) showed a significant improvement of −9.1 (95% CI, −12.8 to −5.3; P
“Looking at individual components of the WOMAC score — pain, stiffness, and physical function — we found these also all significantly improved at the end of the 2-year extension phase,” reported Wagenaar.
She added that after 2 years, there were significant improvements in weight loss (from 94.9 to 92.1 kg), BMI (from 33.3 to 32 kg/m2), and waist circumference (from 110 to 106.7 cm).
By the end of the trial and at 1 year of the extension study, there were significant improvements in A1c, fasting blood glucose, and low-density lipoprotein cholesterol, but at 2 years, these were no longer significant.
Regarding medications use, Wagenaar reported that, overall, there was no net change in use of pain, glucose-lowering, or hypertension medications, but 44% of patients using cholesterol-lowering medications were able to lower their dose or stop them.
Disease Activity Score-28 (DAS28) Improvement and Medication Reduction in RA
Turning to the study of the intervention in patients with RA, 77 people (DAS28 ≥ 2.6 and ≤ 5.1, mild to moderate disease) were randomized to receive either the PFJ intervention in addition to usual care or only usual care (control group). Of these, 48 (62%) from both the intervention and control groups also completed the 2-year follow-up. The details of the PFJ intervention and the extension study for RA were the same as for the OA patient group.
Wagenaar commented on how they tried to individualize the exercise part of the program. “We noticed many of the RA patients asked too much of their body, while in contrast, those with OA were too hesitant,” she said. “We decided to focus on people’s own physical barriers, and we wanted to protect these. Sometimes, people needed to move more, and at other times, we had to tell people to slow down. Often, we advised people to move more by integrating exercise into their daily life.”
Similar to the OA study, patients were asked to try to avoid changing their medications in the 16-week study. “In the extension study, they were encouraged to reduce their medication in collaboration with their rheumatologist,” explained Wagenaar, who monitored any changes.
Differences were quantified according to medication groups comprising rheumatic medications, as well as pain, blood pressure, glucose-lowering, and cholesterol medications, and changes were categorized as increased, stable, or decreased/stopped.
Again, participants were mostly women (92%) with an average age of 55 years, BMI of 26 kg/m2, and DAS28 of 3.85 at baseline. Dropout reasons were similar to those for OA, and over 85% of participants were on medications.
During the 16-week trial period, the DAS28 changed more in the intervention participants than in the controls, and after 2 years of follow-up, DAS28 was significantly lower than baseline with a mean difference of −0.9 (95% CI, −1.2 to −0.6; P
“Comparing with the literature, the drop in DAS28 was similar to that seen with medication, so it’s a very significant reduction,” remarked Wagenaar.
Mean tender joint count dropped from 3 to 0, and general health components of the DAS28 improved significantly over the intervention and over the 2-year follow-up, whereas there was no significant difference in the already low erythrocyte sedimentation rate and swollen joint count compared with baseline. C-reactive protein (CRP) changed from 3.2 to 1.3 mg/L over the 2-year follow-up. High-density lipoprotein increased from 1.6 to 1.8 mmol/L.
A total of 44% of people using antirheumatic medication decreased or stopped them after the 2-year extension.
Wagenaar went on to say that focus group findings suggested that “participants were very enthusiastic about the program despite it largely involving lifestyle change, and this is reflected in our low dropout rates after the trial and 1-year extension [20% for OA and RA].” There were more dropouts in year 2 of the extension.
In an interview with Medscape Medical News, Wagenaar explained why she felt the program had been so well received. “People in the program felt like they had more control over their disease, and they felt listened to.”
Mechanisms Underpinning PFJ
Wagenaar and colleagues also sought to determine the possible mechanisms underlying the clinical effects of the plant-based diet on RA. “With RA, we have the mucosal origins hypothesis, which suggests RA is triggered at the mucosal site [of the gut] in genetically predisposed individuals, and this consequently transfers to the synovial [fluid in] joints,” she said.
“On top of this, we know that fiber protects our gut barrier and therefore reduces inflammation. The PFJ intervention is a very high-fiber program, so our hypothesis is that it might help [strengthen] the barrier,” she explained.
Wagenaar and colleagues collected fecal samples from patients and measured the albumin and calprotectin in them, which are both indicators of the gut barrier function. The researchers analyzed metabolomic data and found that fecal albumin — considered a gut barrier integrity marker — decreased significantly in the intervention group. In patients with RA, this improvement corresponded with an improvement in DAS28, the researchers reported in a poster at the meeting.
“Patients who had the greatest improvement in their gut barrier function also showed the greatest improvement in the DAS28 score, suggestive of a possible link between gut barrier improvement and clinical effects.”
They did not identify any change in calprotectin, an inflammation marker, but Wagenaar said this might change later. “We found that in those on the intervention, at 4 months, the CRP wasn’t reduced, but 1 year later it was.”
The metabolite lenticin, a lentil intake biomarker considered protective against inflammation and osteoclastic differentiation, also increased. Tryptophan was also reduced in people on the PFJ intervention.
Fernando Estevez-Lopez, PhD, a sports scientist at Harvard University, Boston, who specializes in physical activity and behavioral change in rheumatology patients, co-moderated the session and remarked that, “In this study, they did a brilliant job with encouraging participants to follow the program. The design and methods were really good — the sample size was good, and they followed people up. Also, these researchers come from Reade [a medical research center in Amsterdam University Medical Center] where they are well known for applying their research findings to the clinic,” he said.
“In terms of physical activity, we really mean increasing the time spent moving, for example, gentle activity such as walking, or changing behaviors in people with OA and RA. We don’t want them to have more pain the next day.”
Wagenaar reported receiving a grant from ZonMw (The Netherlands Organization for Health Research and Development). She and colleagues hold shares in Plants for Health, a limited liability company. Estevez-Lopez reported having no relevant disclosures.