Blog Pioglitazone and Rheumatoid Arthritis

Recently I’ve read: M.J. Ormseth and colleagues: “Peroxisome proliferator-activated receptor gamma agonist effect on rheumatoid arthritis: a randomized controlled trial.” (Arthritis Res Ther. 2013 Sep 10;15(5):R110. [Epub ahead of print] / http://www.ncbi.nlm.nih.gov/pubmed/24020899). Methods: “In a single center, randomized, double-blind, placebo-controlled, cross-over study patients with RA (n = 34) receiving stable therapy were randomized to also receive either pioglitazone 45 mg daily (n = 17) or matching placebo (n = 17) for 8 weeks.” I haven’t seen a primary endpoint. The conclusion: “Addition of pioglitazone to RA therapy improves insulin resistance and modestly reduces RA disease activity measured by DAS28 CRP and two of its components including patient-reported global health, and CRP; but not DAS28 ESR or ESR.”

I’ve already written on the subject: http://rheumatologe.blogspot.de/2012/12/pioglitazone-at-acr-2012-in-washington.html.

Now, I’ve reread the abstract the same authors published in 2012. Methods: “In a single center, randomized, double blind, placebocontrolled cross-over trial of 20 weeks duration, patients with RA (n_34) and moderate disease activity receiving stable disease modifying anti-rheumatic drug therapy were randomized to receive either pioglitazone 45mg daily (n_17) or matchingplacebo (n_17) for 8 weeks in addition to current therapy.“ And the conclusion: “The addition of pioglitazone to current RA treatment improves insulin resistance and modestly reduces RA disease activity measured by DAS28 CRP and CRP levels.”

So, we don’t have a new study and repeating an old study doesn’t make it more convincing.

I’d like to quote myself:

“Addendum 06.03.2013:

France had withdrawn the approval of pioglitazone because of the increased incidence of bladder cancer. Another problem is the increase of bone loss. This might reduce even more the handiness in treating patients who are already at a risk for bone loss. http://informahealthcare.com/doi/abs/10.1517/14740331003623218

I'll keep it on my list, though I think that Takeda is looking for a new playground for pioglitazone.”

Pioglitazone at the ACR 2012 in Washington

Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, prescribed in diabetes usually, now has been tested in rheumatoid arthritis.

Michelle J. Ormseth and colleagues presented a study: "A Proof-of-Concept Randomized Controlled Trial" (Abstract No. 832). Conclusion by the authors: Pioglitazone "modestly reduces RA disease activity measured by DAS28 CRP and CRP levels". Results speak another language: no significant reduction in swollen or tender joint count, no significant change in ESR or DAS28 ESR, and a non-significant trend toward decreased patient reported disease activity. But lower extremity edema was more common in patients receiving pioglitazone (16%) than placebo (0%).

Wenpu Zhao and colleagues looked into effects of pioglitazone in lupus: "The Peroxisome-Proliferator Activated Receptor-Agonist Pioglitazone Modulates Aberrant T-Cell Responses in Systemic Lupus Erythematosus" (Abstract No. 2499). RNA from treated or untreated SLE patients and controls was extracted and processed on microarrays. In conclusion the authors interpreted their results as indication that peroxisome-proliferator activated receptor-agonist selectively modulate T cell function in SLE.

But in RA patients joints stay tender and swollen, effect is limited to CRP, a reasonable number of patients develops lower extremity edema. Though I can see a rational for testing pioglitazone, I see a possible use for this drug only in patients who suffer from rheumatoid arthritis and diabetes at the same time. Maybe scientific knowledge gains more by messenger RNA testing of T-cell responses than patients or clinicians gain directly. I'll keep it on my list for the next year, but there should be more than just a reduction of CRP.

Addendum 06.03.2013:
France had withdrawn the approval of pioglitazone because of the increased incidence of bladder cancer. Another problem is the increase of bone loss. This might reduce even more the handiness in treating patients who are already at a risk for bone loss. http://informahealthcare.com/doi/abs/10.1517/14740331003623218
I'll keep it on my list, though I think that Takeda is looking for a new playground for pioglitazone.