Meeting News

Earlier treatment with baricitinib improves onset of efficacy

CHICAGO — Patients with moderate to severe rheumatoid arthritis experienced onset of efficacy sooner when treatment with baricitinib started earlier vs. later, although improvement in overall disease activity was similar among patients who received earlier vs. later treatment, according to findings presented at the ACR/ARHP 2018 Annual Meeting.

“Baricitinib [Olumiant, Eli Lilly] is an oral JAK1/JAK2 inhibitor approved for the treatment of moderately to severely active RA in adults in over 40 countries, including European countries, the United States, and Japan,” the researchers wrote. “The objective of this analysis was to assess if patients who receive baricitinib early attain added clinical improvement compared to patients with a delayed start of therapy.”

Peter C. Taylor, MA, BM, BCh , PhD, FRCP, FRCPE, Norman Collison chair of musculoskeletal sciences at University of Oxford, director of clinical sciences at the Arthritis Research UK and NIHR clinical trials unit at the Botnar Research Centre and Kennedy Institute of Rheumatology, and colleagues performed an analysis of the 52-week, phase 3 RA-BEAM study. The RA-BEAM trial demonstrated clinical improvement of once-daily baricitinib 4 mg compared with placebo or adalimumab among patients with inadequate response to methotrexate.

In the RA-BEAM trial, 1,305 patients with a mean disease duration of 8.7 years were randomly assigned 3:3:2 to treatment with placebo, baricitinib 4 mg once per day or adalimumab 40 mg every 2 weeks. Patients with an insufficient response — defined as a lack of 20% or greater reduction in tender and swollen joint count — at week 16 or at successive visits were rescued to open-label treatment with baricitinib 4 mg. At week 24, patients in the placebo group transitioned to treatment with baricitinib 4 mg.

For this analysis, patients first assigned to treatment with baricitinib 4 mg were classified as the early start group. Patients rescued with baricitinib at week 16 or switched from placebo to baricitinib at week 24 or later were considered the delayed start group.

The researchers evaluated differences from baseline with mixed model repeated measures; mean scores were measured for the Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity Score in 28 joints based on high-sensitivity C-reactive protein level (DAS28-hsCRP), DAS28 erythrocyte sedimentation rate (DAS28-ESR), health assessment questionnaire disability index (HAQ-DI) and modified total Sharp score (mTSS) to examine the early vs. delayed start groups between weeks 24 and 52.

More patients in the delayed start group (n = 128; 26.2%) were rescued to baricitinib than in the early start group (n = 35; 7.2%) between weeks 16 and 24.

Patients in the early start group experienced a considerable change from baseline through week 32; these patients also demonstrated an increased reduction in CDAI that occurred more quickly in the first 4 weeks (> 50% reduction) compared with the delayed start group. By week 24, patients in the delayed start group demonstrated a decrease in CDAI scores that was comparable to the decrease seen in the early start group between weeks 4 and 8. This translated to a 4 to 5 month gain in disease improvement for patients in the early start group, according to Taylor and colleagues. Following treatment with baricitinib, patients in the delayed start group also experienced a quick improvement in CDAI scores; by week 40, results in these patients matched the results seen in the early start group.

The researchers observed comparable results for SDAI, DAS28-ESR, and DAS28-hsCRP, although the early start group demonstrated substantially better improvement in HAQ-DI that was maintained at week 40, as well as a substantial advantage from weeks 16 to 52 in regard to mTSS.

“While overall disease activity improvement was similar, early start of baricitinib treatment provided faster efficacy,” the researchers wrote. “A delay of up to 6 months in baricitinib treatment had an impact on HAQ-DI and structural damage progression.” - by Julia Ernst, MS

Disclosures: Taylor reports personal fees from AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck, Pfizer and Takeda; grant support from Celgene and Galapagos; and grant support and personal fees from UCB Pharma. Please see the abstract for all other authors’ relevant financial disclosures.

Reference:

Taylor PC, et al. Abstract 546. Presented at ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.

CHICAGO — Patients with moderate to severe rheumatoid arthritis experienced onset of efficacy sooner when treatment with baricitinib started earlier vs. later, although improvement in overall disease activity was similar among patients who received earlier vs. later treatment, according to findings presented at the ACR/ARHP 2018 Annual Meeting.

“Baricitinib [Olumiant, Eli Lilly] is an oral JAK1/JAK2 inhibitor approved for the treatment of moderately to severely active RA in adults in over 40 countries, including European countries, the United States, and Japan,” the researchers wrote. “The objective of this analysis was to assess if patients who receive baricitinib early attain added clinical improvement compared to patients with a delayed start of therapy.”

Peter C. Taylor, MA, BM, BCh , PhD, FRCP, FRCPE, Norman Collison chair of musculoskeletal sciences at University of Oxford, director of clinical sciences at the Arthritis Research UK and NIHR clinical trials unit at the Botnar Research Centre and Kennedy Institute of Rheumatology, and colleagues performed an analysis of the 52-week, phase 3 RA-BEAM study. The RA-BEAM trial demonstrated clinical improvement of once-daily baricitinib 4 mg compared with placebo or adalimumab among patients with inadequate response to methotrexate.

In the RA-BEAM trial, 1,305 patients with a mean disease duration of 8.7 years were randomly assigned 3:3:2 to treatment with placebo, baricitinib 4 mg once per day or adalimumab 40 mg every 2 weeks. Patients with an insufficient response — defined as a lack of 20% or greater reduction in tender and swollen joint count — at week 16 or at successive visits were rescued to open-label treatment with baricitinib 4 mg. At week 24, patients in the placebo group transitioned to treatment with baricitinib 4 mg.

For this analysis, patients first assigned to treatment with baricitinib 4 mg were classified as the early start group. Patients rescued with baricitinib at week 16 or switched from placebo to baricitinib at week 24 or later were considered the delayed start group.

The researchers evaluated differences from baseline with mixed model repeated measures; mean scores were measured for the Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity Score in 28 joints based on high-sensitivity C-reactive protein level (DAS28-hsCRP), DAS28 erythrocyte sedimentation rate (DAS28-ESR), health assessment questionnaire disability index (HAQ-DI) and modified total Sharp score (mTSS) to examine the early vs. delayed start groups between weeks 24 and 52.

More patients in the delayed start group (n = 128; 26.2%) were rescued to baricitinib than in the early start group (n = 35; 7.2%) between weeks 16 and 24.

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Patients in the early start group experienced a considerable change from baseline through week 32; these patients also demonstrated an increased reduction in CDAI that occurred more quickly in the first 4 weeks (> 50% reduction) compared with the delayed start group. By week 24, patients in the delayed start group demonstrated a decrease in CDAI scores that was comparable to the decrease seen in the early start group between weeks 4 and 8. This translated to a 4 to 5 month gain in disease improvement for patients in the early start group, according to Taylor and colleagues. Following treatment with baricitinib, patients in the delayed start group also experienced a quick improvement in CDAI scores; by week 40, results in these patients matched the results seen in the early start group.

The researchers observed comparable results for SDAI, DAS28-ESR, and DAS28-hsCRP, although the early start group demonstrated substantially better improvement in HAQ-DI that was maintained at week 40, as well as a substantial advantage from weeks 16 to 52 in regard to mTSS.

“While overall disease activity improvement was similar, early start of baricitinib treatment provided faster efficacy,” the researchers wrote. “A delay of up to 6 months in baricitinib treatment had an impact on HAQ-DI and structural damage progression.” - by Julia Ernst, MS

Disclosures: Taylor reports personal fees from AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck, Pfizer and Takeda; grant support from Celgene and Galapagos; and grant support and personal fees from UCB Pharma. Please see the abstract for all other authors’ relevant financial disclosures.

Reference:

Taylor PC, et al. Abstract 546. Presented at ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.

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