Two Prescriptions, One Patient Save

Obesity, in particular in psoriatic arthritis (PsA) was widely covered at #ACR26. This is from the recognition of the size of the problem. In the Swiss SCQM registry, 63.6% of 2,087 patients with PsA were overweight or obese, against 31% overweight and 12% obese in the Swiss population, and higher BMI tracked disease activity, cardiometabolic disease and depression [2014]. US health record data covering 19.9 million people point the same way [2015]. Obesity is not background noise in PsA. It is part of the disease landscape.

TOGETHER PsA reported its 52 week results  [2942] where 271 adults with active PsA and overweight or obese were randomised one to one, 138 to ixekizumab plus tirzepatide and 133 to ixekizumab alone, open label, at US approved doses. Mean age 55, 69.7% women, mean BMI 37.6, and 18.8% had already failed two or more classes of advanced therapy.

At week 52, ACR50 was reached by 43.7% on the combination against 15.7% on ixekizumab alone, a difference of 28.0 percentage points, 95% CI 17.1 to 38.9, p <0.001. The primary endpoint at week 36, ACR50 together with at least 10% weight loss, had been met at 31.7% against 0.8%, and by week 52 that composite stood at 39.2% against 1.7%. ACR20, minimal disease activity, DAPSA, hsCRP and HAQ DI all favoured the combination, as did weight, systolic blood pressure, triglycerides and total cholesterol. Pooled with TOGETHER PsO, the combination also improved complete skin clearance and lowered HbA1c, triglycerides and blood pressure at week 36 [2298].

What is genuinely interesting and TOGETHER PsA supplies the clue rather than the answer is the separation in ACR50 that appeared by week 4, before any clinically meaningful weight loss had occurred. Whatever is driving the joint response, it does not wait for the scales.

In a small Erlangen cohort, add on tirzepatide reduced pain by 34 to 46 points on a 100 point scale, but it did so in non-psoriatic arthralgia as well as in PsA [0346]. That points to load and adiposity. In a Toronto matched cohort, each month of GLP1 RA use was linked to lower cDAPSA and pain even after adjusting for BMI change [0373]. Population data agree on direction: GLP1 RA prescription was associated with fewer joint effusions and steroid injections over three years [1302], Both mechanisms may be true at once.

Over a fifth of US patients on bimekizumab for PsA or axSpA were already taking an incretin [1304]. In a Toronto cardio rheumatology clinic, 56.7% of PsA patients met GLP1 RA eligibility and only 15.7% of those eligible were prescribed one [0361]. US rheumatologists estimate use in 14% of their PsA patients and now name IL17 inhibitors as the preferred partner [1315]. The biologic data explain why it matters: on bimekizumab, ACR50 at three years was 41.0% with BMI 35 or above against 56.8% in the lightest group studied [1305], while cardiometabolic markers improved and no adjudicated MACE occurred in axSpA over three years [0350]. Effective immune therapy helps, but it does not close the BMI gap on its own.

Access to incretins may depend on obesity criteria and funding of the treatment, not on rheumatological need. The question is no longer whether weight belongs in the rheumatology consultation. It is who writes the second prescription, and who pays for it. 

A modelling study of clinical and economic outcomes with this combination [2715] will matter to those asked to fund it. The task is practical: joint pathways with pharmacy, dermatology and weight management services, outcome measures that include weight and pain, and an evaluation of who benefits most. 

Patients do not need two clinicians writing two prescriptions in two buildings. They need one plan. That may prove the most useful for patients with psoriatic disease.