Beni Toure

A new study into the effects of sarilumab on HbA1c and fasting glucose is offering clinicians additional insight on the treatment of patients 

Results of the study, which compared treatment of patients with rheumatoid arthritis and diabetes with sarilumab, adalimumab, and placebo therapies, were presented at the 

Clinical Congress of Rheumatology (CCR) West 2019 annual meeting in San Diego, CA

In an effort to assess the effects of sarilumab on HbA1c, investigators conducted a post hoc analysis of 2, 24-week trials. The 2 trials included in the analysis were the TARGET (NCT01709578) trial and the MONARCH (NCT02332590) trial.

The TARGET trial was a study examining sarilumab—in 150/200 mg doses every two weeks&mdash; against placebo in patients who were intolerant or had an indequate response to anti-TNF treatment. Monarch was a monotherapy trial examining sarilumab 200 mg every 2 weeks compared with adalimumab 40 mg every 2 weeks in patients who were intolerant or had an inadequate response to methotrexate and were biologic disease-modifying antirheumatic drug naive.

TARGET involved 546 patients, of which 67 (12.3%) had diabetes. MONARCH included 369 patients, of which 26 (7%) had diabetes. Investigators noted diabetes was defined as a medical history of diabetes or concomitant use of antidiabetic treatment.

At 24 weeks, investigators noted differences in least-squares mean change from baseline in HbA1c between the three groups. Mean change from was with sarilumab 150/200 mg was -0.24%/-0.44% compared to +0.23% with placebo in TARGET. In MONARCH, investigators noted mean least-squares change of -0.28% with sarilumab compared to +0.15% with adalimumab monotherapies.

Patients with baseline IL-6 greater than 37.5 pg/mL treated with sarilumab had greater reductions in HbA1c then those with baseline IL-6 equal to or less than 37.5 pg/mL (least-squares mean change -0.27 versus -0.13).

Investigators pointed out there was no observed interaction between HbA1c and baseline glucocorticoid use. Additionally, changes in HbA1c did not correlated with changes in C-reactive protein, Disease Activity Score 28-joint count C-reactive protein, or hemoglobin.

Investigators suggested results of the study had multiple clinical implications. Those implications included patients with rheumatoid arthritis and diabetes saw greater improvement in HbA1c with sarilumab than with adalimumab or placebo and changes in HbA1c were not impacted by baseline glucocorticoid use.

“Patients with RA and diabetes treated with sarilumab had greater improvements in HbA1c than with adalimumab or placebo,” investigators wrote. “With monotherapy, differences between sarilumab and adalimumab were more pronounced among patients with higher baseline IL-6 level.”

This study, “Effect of Sarilumab on Glycosylated Hemoglobin in Patients with Rheumatoid Arthritis and Diabetes,” was presented at CCR West.

Articles

A post hoc analysis presented at CCR West found sarilumab outperformed adalimumab and placebo in HbA1c improvement in rheumatoid arthritis patients with diabetes.

For HbA1c in RA Patients, Sarilumab Outperforms Adalimumab, Placebo

Baricitinib (OLUMIANT) has met primary endpoint marks in its most recent pivotal phase 3 trial designed to assess the Janus kinase (JAK) inhibitor for the treatment of moderate to severe adult 

Recent findings from the third phase 3 trial in the BREEZE-AD program, to be fully completed later this year, show baricitnib plus standard-of-care topical corticosteroids significantly improved patient disease severity per validated Investigator’s Global Assessment for atopic dermatitis (vIGA) score of “clear” or “almost clear” skin (vIGA 0, 1) at 16 weeks.

The trial is currently being conducted outside of the US, and marks the midway point of the planned 5 placebo-controlled phase 3 studies from Eli Lilly and Company that will assess barictinib.

A total of 329 patients were randomized 1:1 to either baricitnib 2 mg (n = 109), 4 mg (n = 111), or placebo (n = 109), plus corticosteroids. At week 16, 23.9% and 30.6% of patients administered baracitnib 2 mg and 4 mg achieved vIGA 0 or 1, respectively (

≤ .01). Just 14.7% of patients administered placebo achieved either mark.

A significantly greater rate of patients on baricitnib 2 mg (43.1%; 

≤ .001) also achieved Eczema Area and Severity Index improvement of at least 75% (EASI75) at week 16, compared to just 22.9% of placebo patients.

The safety data for baricitnib were consistent with the therapy’s known profile, and the most common treatment-emergent adverse events included nasopharyngitis, upper respiratory tract infection and folliculitis. No patients reported major adverse cardiovascular events, malignancies, or deaths during the trial.

The findings follow the successful BREEZE-AD1 and BREEZE-AD2 clinical trials from earlier this year, and precede the remaining 2 phase 3 trials to be announced in late 2019 or 2020.

Baricitinib is currently approved for adults with moderately to severely active 

Lotus Mallbris, MD, PhD, vice president of Immunology Development for Lilly, said in a 

 that moderate to severe atopic dermatitis persists as a significantly unmet disease clinically, despite recent advances in the field.

“Atopic dermatitis is a chronic, relapsing condition that can vary greatly from person to person, and yet there are few medicines to address the different signs and symptoms in each patient," Mallbris said. "Today's baricitinib results in combination therapy reveal important additional clinical information in a chronic disease where patients currently have limited oral treatment options." 

The JAK inhibitor previously approved for rheumatoid arthritis has reported early primary endpoint outcomes in its ongoing phase 3 trial.