Is Obesity Inflating Your Disease Activity Scores? Save

Obesity is common in inflammatory arthritis, with an estimated 60-70% of people with rheumatoid arthritis and 70-80% of people with psoriatic arthritis also living with overweight or obesity. But does obesity affect disease activity and outcomes in inflammatory arthritis? Dr. Michael George, MD, MSCE, will take on that question in the session "Size Matters: Optimizing Therapy and Outcomes for Patients with Obesity and Rheumatic Disease" today, Monday, Nov. 9th.

Worse scores, similar images

Dr. George illustrates that obesity changes disease activity scores more than it changes the synovium. In NORD-STAR, which randomized 793 patients with early RA, those with obesity were less likely to reach DAS28 remission in every arm, including csDMARDs, certolizumab, abatacept and tocilizumab. In CorEvitas (5,901 patients starting a biologic), both obese and underweight patients were less likely to reach low disease activity, with similar patterns for TNF and non-TNF agents.

Imaging tells a different story. 

In 1,068 patients from two golimumab trials, obesity went with less bone edema on MRI and less radiographic progression at 52 or 104 weeks. A Leiden cohort of 454 patients also showed less osteitis and slower erosion progression. The gap is driven by patient global, pain, function and tender joint count, and CRP runs higher with obesity in the general population too. His message: remission is harder to reach whichever drug is chosen, yet inflammatory activity is not worse.

Should obesity steer drug choice? His argue no: a patient who misses remission on a TNF inhibitor because of pain and fatigue rather than swollen joints is unlikely to do better on a different mechanism.

Will weight loss help?

In psoriatic arthritis, TOGETHER-PsA randomized 271 adults with obesity or overweight (mean BMI 37.6) to ixekizumab with or without tirzepatide. Joseph Merola, MD, will present 52-week results (abstract 2942, Wednesday, Nov 11): ACR50 of 43.7% versus 15.7%, ACR20 of 73.3% versus 35.8%, and weight change of -20.4% versus -0.6%. The trial was open-label with assessor blinding, only week 36 ACR50 was multiplicity-controlled, and treatment discontinuation was 36.8% with ixekizumab alone versus 20.3% with the combination. Nausea occurred in 29.7% versus 3.0%.

Abstract 0346 shows an interim analysis of 15 overweight adults (5 with PsA, 5 with psoriasis, 5 with arthralgia but neither condition) given tirzepatide (a dual receptor agonist that activates both GIP - glucose-dependent insulinotropic polypeptide - and GLP-1) for 24 weeks. Mean pain VAS fell by 33.8, 40.0 and 46.0 points, with weight loss of 14.7, 19.0 and 12.2 kg at the latest timepoints reported. Baseline swollen joint counts were 0.0 in every group, so the pain treated was not obviously synovitis, which speaks directly to Dr George's question of symptoms versus inflammation. 

In addition to pharmacologic management, bariatric surgery is another option for weight loss. In RA, weight loss may benefit fatigue, pain, CRP and DAS28, though perhaps not synovitis or damage. After gastric bypass, 53 patients with RA had lower CRP, less medication use and higher remission rates, and in the SOS cohort of 4,047 people surgery lowered psoriasis risk but not RA risk. Four RA abstracts on GLP-1 receptor agonists (484 on Sunday, Nov 8; 1038, 1410 and 1445 on Monday, Nov 9) will add real-world data.

In summary, obesity can make remission harder to reach and symptoms harder to treat without meaning more synovitis, so the target matters as much as the drug. Weight loss is worth pursuing for symptoms and function, but whether it quiets joint inflammation, and whether it does so equally in psoriatic and rheumatoid disease remains an open question.