Anti-TNFs in PsA

Patients with psoriatic arthritis who met minimal disease activity with golimumab treatment at three or…

It’s a classical case of “success breeding success, failure foreboding failure”.
Given the increasingly wide array of “effective” treatments available to PsA patients, and the sorely lacking availability of reliable biomarkers of response to various therapies, we should at least mitigate our therapeutic guesswork by moving through the options quickly.
Sitting through a 3-4 months’ trial-&-error is unacceptable: at the expense of disease progression and damage if a particular drug doesn’t work, and at the expense of, well, substantial financial expense. To me, it should be 1 shot of a biologic to either make it or break it.

Methotrexate Yields No Added Benefit in Etanercept Treated Psoriatic Arthritis Patients

Despite a paucity of clinical trial proof, methotrexate is often advocated or mandated to treat psoriatic arthritis.  A recent comparison of clinical trials outcomes fails to show any added value when MTX is given to PsA patients taking etanercept.

Unlike the case with RA, combination of MTX with an anti-TNF conferred no additional efficacy benefit in the treatment of PsA.

LONDON – Patients with psoriatic arthritis appear less likely to achieve a good response to their first anti–tumor necrosis factor (anti-TNF) therapy if they are…|By SARA FREEMAN

Anti-TNF therapy appears less effective in obese patients and in those who gain weight in the course of their treatment (personal anecdotal observation).
Possible reasons include:
1) increased volume of distribution “dilutes” drug concentration;
2) adipose tissue is pro-inflammatory;
3) lesser efficacy leads to poorer drug-adherence.

When secondary inadequate response happens to my patients, I embark on the following:
1) re-evaluate for development of other Metabolic Syndrome and endocrine conditions worsening weight gain (esp obstructive sleep apnoea);
2) evaluate for dysbiosis (eg stool calprotectin) possibly driving inflammation;
3) consider adding a csDMARD (eg MTX, Leflunomide), despite the lack of data of efficacy of combination therapy (I’ll speculate in a later post why such studies seem ineffective);
4) consider switching from an anti-TNF to an anti-IL17 or anti-IL12/23, or combining the 2 classes (dual-specific monoclonals are currently in development);
5) other options include Tofacitinib and Apremilast.

This will be complemented by much nagging to lose weight through healthier diet and regular exercise. Bariatric surgery is not off limits either.