Consistent clinical outcomes have been achieved using both the originator infliximab (IFX) and a biosimilar infliximab in patients with inflammatory bowel disease (IBD), an international expert has told Australian clinicians.

Furthermore, immune responses to the biosimilar infliximab ‘Inflectra’ very closely resemble those to the originator product ‘Remicade®’, Dr Milan Lukáš, from the IBD Clinical Research Centre at Charles University in Prague, Czech Republic told delegates attending a symposium hosted by Pfizer.

“A biosimilar is another version of an already licensed biologic, with no meaningful differences from the reference medicinal product in terms of quality, physicochemical properties, biologic activity, safety or efficacy based on comprehensive comparability processes,” Dr Lukáš said.

The biosimilar infliximab CT-P13 (marketed in Australia as Inflectra) was licensed in Europe for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC) in September 2013.

“The decision was based on extrapolation of data from its use in ankylosing spondylitis and rheumatoid arthritis to IBD, and the need for increased access to effective biologic therapies,” he said.

“Biosimilar IFX is effective and well tolerated in patients with CD and UC,^1,2 and has been shown to induce mucosal healing in UC.³ Switching from originator infliximab to CT-P13 for the treatment of IBD is feasible in clinical practice.^4,5

In addition, originator infliximab and CT-P13 have similar immunogenicity and shared immunodominant epitopes” ⁶ he told symposium delegates.

Experience from three studies

Dr Lukáš presented data from three studies on the use of Inflectra in his unit. The first evaluated the efficacy and safety of Inflectra in 90 patients with Crohn’s disease (CD) and 29 patients with ulcerative colitis (UC) who had not previously been treated with anti-TNF therapy.

A report on the first 104 patients in the series was presented at the European Crohn’s and Colitis Organisation (ECCO) 2016 annual conference.⁷

The 119 patients in the updated dataset had a median disease duration of about 6.5 years, and 31% of the CD patients had perianal disease.

An intention-to-treat analysis at week 14 identified complete responses in 27.8% and 24.1% of the CD and UC patients respectively. Partial responses were identified in another 62.2% and 51.7% of CD and UC patients respectively. An endoscopic response (Mayo endoscopic score grade 0 or 1) was obtained in 50% of UC patients at week 14.

At week 38:

• complete or partial responses were obtained in 59% of patients with CD and 59% of patients with UC
• perianal disease was resolved in 47.4% of CD patients who had it at baseline, and it was improved in a further 36.8%
• C-reactive protein and faecal calprotectin levels improved significantly in both CD and UC patients
• Antibodies to infliximab developed in 8.6% of patients
• the use of both systemic and topical corticosteroids declined significantly in both CD and UC patients.

“There were no new safety signals compared to previous experience with originator infliximab,” Dr Lukáš said. “We concluded that biosimilar infliximab is effective and safe in IBD patients naive to anti-TNF therapy.”

The second study described 56 patients with CD and 18 patients with UC who were switched to Inflectra after being treated with Remicade® for a median of 3.0 years.⁸

The majority of patients (69%) at the time of switch were in clinical remission. When reviewed after 24 weeks, there was no significant difference in C-reactive protein or faecal calprotectin levels compared to baseline.

There was also no increase in immunogenicity, as assessed by infliximab trough levels and anti-drug antibodies. Disease activity was stable.

Three patients discontinued infliximab, one each because of loss of response, an adverse event, and a low-grade dysplastic lesion in the colon.

No patient experienced an infusion reaction, and the frequency and type of adverse events were similar to that observed during treatment with originator infliximab.

“We have now followed the cohort for a total of 56 weeks and the results remain consistent,” Dr Lukáš said. “The rate of clinical response improved in UC patients and has been maintained in CD patients.”

The third study compared the immunogenicity of Remicade® (n=71) and Inflectra™ (n=60) in patients previously untreated with infliximab.⁹

There was no significant difference between the groups in the proportion of patients with positive anti-drug antibodies or antinuclear antibodies at week 2.

No patients were positive for other markers of immunogenicity including anti-double-stranded DNA or anti-extractable nuclear antigens. The results were similar at week 14.

“These results demonstrate that original and biosimilar infliximab have comparable immunogenicity in patients with IBD in the short-term,” Dr Lukáš said.

References

1. Gecse KB et al. Efficacy and safety of the biosimilar infliximab CT-P13 treatment in inflammatory bowel diseases: A prospective, multicentre, nationwide cohort. J Crohns Colitis 2016; 10: 133-40.
2. Jahnsen J et al. Biosimilar infliximab (CT-P13) in the treatment of inflammatory bowel disease: A Norwegian observational study. Expert Rev Gastroenterol Hepatol 2015; 9 (Suppl 1): 45-52.
3. Farkas K et al. Efficacy of infliximab biosimilar CT-P13 induction therapy on mucosal healing in ulcerative colitis. J Crohns Colitis 2016 Apr 21. pii: jjw085. [Epub ahead of print]
4. Smits LJ et al. Clinical outcomes following a switch from Remicade® to the biosimilar CT-P13 in inflammatory bowel disease patients: a prospective observational cohort study. J Crohns Colitis 2016 Apr 19. pii: jjw087.
5. Kolar M et al. Switching of patients with inflammatory bowel disease from original infliximab (Remicade®) to biosimilar infliximab (Remsima™) is effective and safe. Poster presented at ECCO 2016. DOP032.
6. Ben-Horin S et al. Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima. Gut 2016; 65: 1132-8.
7. Bortlik M et al. Biosimilar infliximab is effective and safe in inflammatory bowel disease patients naïve to anti-TNF therapy: a tertiary centre experience. Poster presented at ECCO 2016. P495.
8. Kolar M et al. Switching of patients with inflammatory bowel disease from original infliximab (Remicade®) to biosimilar infliximab (Remsima™) is effective and safe. Poster presented at ECCO 2016. DOP032.
9. Malickova K et al. No difference in immunogenicity of the original and biosimilar infliximab in patients with inflammatory bowel disease: short-term results. Poster presented at ECCO 2016. P311.