New Studies Investigate Infliximab Biosimilars in Treating CD, UC, and RA

At the recent European Crohn's and Colitis Organisation’s 13th Congress in Vienna, Austria, several studies investigated the efficacy of infliximab biosimilars in treating Crohn disease (CD), ulcerative colitis (UC), and rheumatoid arthritis (RA).

Biosimilar Infliximab Improved Cachexia, as Did Adalimumab

CD in some pediatric and adolescent patients presents with cachexia, which manifests as malabsorption, nutritional deficiencies, osteopenia, sarcopenia, and growth failure. Researchers investigated whether adalimumab (Humira) or a biosimilar infliximab (CT-P13, sold in Europe as Remsima) in an animal model could reduce symptoms of cachexia.¹

Both adalimumab and biosimilar infliximab were administered 3 times per week in mice xenografted with C26 adenocarcinoma cells for up to 3 weeks of maintained cachexia.

Researchers found that both adalimumab and infliximab significantly improved cancer cachexia, presenting with significantly lowered mortality, tempered weight loss, and preserved appetite.

Specific genes, including PAX7, as well as muscle-related genes, such as MurF-1, artrogin-1, and Mul-1, were significantly reduced, along with significantly decreased tumor necrosis factor (TNF) serum levels (P <.01).

The researchers say that “top-down” administration of biologics targeting TNF should be considered for treatment of pediatric or adolescent patients with CD presenting with severe wasting conditions.

CT-P13 Has “Strong Positive Impact on Quality of Life”

Another study involving CT-P13 evaluated the safety and effectiveness of the biosimilar infliximab when administered in a real-world setting in adults with active CD or UC.

This was a non-interventional trial conducted in Romania, Czech Republic, and Bulgaria in patients with moderate to severe active CD that was unresponsive to steroids and/or immunosuppressive agents, and in patients with moderate to severe active UC that responded inadequately to conventional therapy.

Participants received biosimilar infliximab at the start of the study, week 2, week 6, week 12, week 14, week 22, and week 30. Safety was assessed by adverse events (AEs) and early withdrawals. Effectiveness was assessed at the start and conclusion of the trial, as well as early withdrawal visits using the Crohn Disease Activity Index (CDAI) for patients with CD and the partial version without endoscopy of the Clinical Activity Index (pCAI) for patients with UC. Quality of life was measured by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ).

There were 84 participants with 24 identified AEs: 2 were adverse drug reactions of moderate severity, and 22 were considered unrelated to biosimilar infliximab. A total of 17 patients withdrew prematurely.

In total, 67 patients (CD: 31; UC: 36) had baseline and follow-up effectiveness measurements. The researchers found the following:

• Patients showed significant improvements in disease activity relative to baseline in terms of mean CDAI score (329 at baseline versus 176 at end of treatment)
• Patients also showed significant improvements in disease activity relative to baseline in terms mean pCAI score (9.4 at baseline versus 2.7 at end of treatment)
• The response rate was 71% in the CD group and 59% in the UC group
• The remission rate was 52% in the CD group and 57% in the UC group
• Mean SIBDQ was significantly improved in the combined group (4.0 at baseline versus 5.6 at the end of treatment)

“In real-life setting, biosimilar infliximab was safe and improved disease activity and had a strong positive impact on quality of life in patients with CD or UC,” say the authors.

Ixifi and Reference Infliximab: Similar Immunogenicity

A multi-national, randomized, double-blind, parallel-group study³ compared the efficacy, safety, and immunogenicity of PF-06438179 (recently approved by the FDA as Ixifi), with that of the European-licensed reference infliximab in adult patients with moderate to severe active rheumatoid arthritis (RA) who were receiving methotrexate.

Patients received an intravenous 3 mg/kg dose of the biosimilar treatment at weeks 0, 2, and 6, then every 8 weeks, with a dose increase to 5 mg/kg allowed from week 14 for inadequate responders. The primary endpoint was a 20% or greater improvement according to American College of Rheumatology Response (ACR20) at week 14.

In total, 650 patients were randomized to receive either the biosimilar (n = 324) or the reference product (n = 326). Anti-drug antibodies (ADAs) were observed in 48.6% of patients treated with the biosimilar and 51.2% treated with the reference up to 30 weeks and normoactive bowel sounds were present in 79% and 85.6% of patients, respectively. The ACR20 response rates at weeks 14 and 30 were similar between treatments regardless of ADA status.

In each treatment group, 83 patients received dose escalation during the first 30 weeks of treatment and, in these patients, the ADA rates at week 30 were similar (45.8% versus 38.6% for the biosimilar and reference groups, respectively) and comparable to those patients not undergoing dose escalation (40.8% versus 46.1%, respectively).

Up to week 30, infusion-related reactions (IRRs) occurred in 5.9% of patients taking the biosimilar and 6.4% of patients taking the reference. In patients with ADAs, IRRs occurred in 7% of the biosimilar group and 8.4% of the reference group.

References

1. Hahm KB, Han YM, Park JM, Kang EA. Adalimumab and infliximab biosimilar ameliorated cachexic syndrome of Crohn disease. Presented at the European Crohn's and Colitis Organisation Congress 2018 meeting, February 14 to February 17, 2018; Vienna, Austria. Abstract P089. www.ecco-ibd.eu/publications/congress-abstract-s/abstracts-2018/item/p089-adalimumab-and-infliximab-biosimilar-ameliorated-cachexic-syndrome-of-crohn-disease.html

2. Gheorghe C, Svoboda P, Dimitriu A, Mateescu B, Kotzev I. Effectiveness and safety of biosimilar infliximab (Remsima) in a real-life setting in 84 patients with Crohn disease and ulcerative colitis. Presented at the European Crohn's and Colitis Organisation Congress 2018 meeting, February 14 to February 17, 2018; Vienna, Austria. Abstract P420. www.ecco-ibd.eu/publications/congress-abstract-s/abstracts-2018/item/p420-effectiveness-and-safety-of-biosimilar-infliximab-remsima-in-a-real-life-setting-in-84-patients-with-crohn-x2019-s-disease-and-ulcerative-colitis.html

3. Palaparthy R, Schmitt S, Rehman MI, Cai CH, Wang K, Von Richter O. Incidence and impact of immunogenicity in a randomized, double-blind phase III study comparing a proposed infliximab biosimilar (PF-06438179/GP1111) with reference infliximab. Presented at the European Crohn's and Colitis Organisation Congress 2018 meeting, February 14 to February 17, 2018; Vienna, Austria. Abstract P554. www.ecco-ibd.eu/publications/congress-abstract-s/abstracts-2018/item/p554-incidence-and-impact-of-immunogenicity-in-a-randomised-double-blind-phase-iii-study-comparing-a-proposed-infliximab-biosimilar-pf-06438179-gp1111-with-reference-infliximab.html