FDA Approves Adalimumab Biosimilar -But Will Enter U.S. Market in 2023!

October 31, 2018: FDA Approves Sandoz’s Biosimilar Adalimumab, Hyrimoz

An excerpt:

The FDA has approved Sandoz’s biosimilar adalimumab, Hyrimoz (adalimumab-adaz). 

The drug has been approved to treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn disease, ulcerative colitis, and plaque psoriasis…

Despite today’s approval, US patients will have to continue to wait for access to Hyrimoz, as the biosimilar will not enter the US market until 2023. Earlier this month, Sandoz announced a global settlement of patent disputes with AbbVie over the drug. While the settlement allowed Sandoz to launch Hyrimoz in the European Union on October 16, 2018, it forestalled US market entry until September 30, 2023. 

My take: Why will this biosimilar be allowed in Europe but not U.$?

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Big Biosimilar Study

Briefly noted: A Meyer et al. Ann Intern Med. 2018. DOI: 10.7326/M18-1512

Abstract link: Effectiveness and Safety of Reference Infliximab and Biosimilar in Crohn Disease: A French Equivalence Study

In this study with 5050 patients, based on review of an administration database, the authors found the following:

  • In multivariable analysis of the primary outcome, CT-P13 (biosimilar) was equivalent to infliximab reference product (RP) (HR, 0.92 [95% CI, 0.85 to 0.99]). 1147 patients in the RP group and 952 patients in the CT-P13 group met the composite end point (including 838 and 719 hospitalizations, respectively).
  • No differences in safety outcomes were observed between the 2 groups: serious infections (HR, 0.82 [CI, 0.61 to 1.11]), tuberculosis (HR, 1.10 [CI, 0.36 to 3.34]), and solid or hematologic cancer (HR, 0.66 [CI, 0.33 to 1.32]).

The authors conclude that “real-world data indicates that the effectiveness of CT-P13 is equivalent to that of RP for infliximab-naive patients with CD.”

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Another Reason For HPV Vaccine –Prevention of Anal Cancer

Briefly noted: A recent study (L Vuitton et al. Clin Gastroenterol Hepatol 2018; 16: 1768-76) document a high prevalence of anal canal high-risk human papillomavirus (HPV)  infection in all subjects (n=469, median age 54 years) and even higher rates in patients with Crohn’s disease (n=70).  The authors detected HPV DNA in anal tissues from 34% of the subjects and high risk (oncogenic) HPV in 18%.  In patients with Crohn’s disease, high risk HPV was detected in 30%.

My take: HPV infection predisposes to anal cancer which represent 3-4% of lower-digestive tract cancers. The high rate of HPV

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Fish Oil for Ulcerative Colitis?

A small randomized, double-blind, placebo-controlled study (E Scaioli et al. Clin Gastroenterol Hepatol 2018; 16: 1268-75) examined the use of Eicosapentaenoic acid-Free Fatty Acid Form (EPA-FFA) a component of n-3 fish oil for patients with ulcerative colitis UC).

From 2014-2016, the investigators enrolled 60 patients who had partial Mayo score <2 and fecal calprotectin >150 mcg/g who had been receiving stable therapy for at least 3 months.  Then they were randomized 1:1 to receive EPA 1000 mg BID or placebo for 6 months.

Key findings:

  • 19 of 30 (63%) EPA-FFA group compared with 4 of 30 (13.3%) of placebo-treated group had achieved the primary endpoint of a 100-point reduction in fecal calprotectin at 6 months.  OR 12.0, P<.001
  • The secondary endpoint of clinical remission was noted in 23 of 30 (77%) in the EPA-FFA group compared with 15 of 30 (50%), OR 3.29, P=.035)
  • No serious adverse effects were reported.


  • Small number of patients from a single center
  • Short follow-up
  • In those without clinical relapse, a followup colonoscopy was not performed

My take: In this study EPA-FFA was associated with lower calprotectin and higher rates of remaining in remission.  More data are needed.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

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FDA IBD Workshop -Take-Home Points

From a previous blog lecture from Athos Bousvaros (NASPGHAN Postgraduate Course 2014)

Off-label does not equate to experimental

FDA Statement: The FD&C Act does not, however, limit the manner in which a physician may use an approved drug. Once a product has been approved for marketing, a physician may prescribe it for uses or in treatment regimens or patient populations that are not included in approved labeling. Such “unapproved” or, more precisely, “unlabeled” uses may be appropriate and rational in certain circumstances, and may, in fact, reflect approaches to drug therapy that have been extensively reported in medical literature.

A Bunch of Data on Vedolizumab

DE Yung et al. Inflamm Bowel Dis 2018; 24: 2327-38.  This systematic review and meta-analysis of four studies “did not detect an increased risk of postoperative complications with preoperative vedolizumab” (VDZ).  This study included 281 patients who received VDZ.

SC Ng et al. Inflamm Bowel Dis 2018; 24: 2431-41. The authors examined the frequency of opportunistic infection among 4 VDZ trials and postmarketing surveillance, accounting for ~114,000 patient-years of exposure. The most common infection was C difficile (0.5 per 100 patient-years); tuberculosis was reported at 0.1 per 100 patient years. This study showed “that the rate of serious opportunistic infections in patients receiving VDZ was low and most patients could continue VDZ treatment.”

SL Gold et al. Gastroenterol 2018; 155: 981-2. This clinical image showed a case of Henoch-Schonlein Purpura (HSP) that developed in a 53 year receiving VDZ.

E Shmidt et al. Inflamm Bowel Dis 2018; 24: 2461-7.  This retrospective review of a prospectively maintained IBD registry provides information of risk factors for VDZ loss of response and management. 444 patients out of 788 who received VDZ had a significant response.The majority of VDZ recipients 75) had failed prior anti-TNF Rx. Key points:

  • Loss of response (LOR) at 6 months and 12 months was 20% and 35% respectively
  • UC patients compared to Crohn’s disease (CD) patients were more likely to have LOR with R of 1.54.
  • Shortening VDZ infusion interval from q8 weeks to q4-6 weeks recaptured response in 49% and led to remission in 18% of this cohort.
  • LOR was more common (2-fold) among those who had a LOR to anti-TNF agent. Patients with primary nonresponse were less likely to have LOR with VDZ.

U Kopylov et al. Inflamm Bowel Dis 2018; 24: 2442-51. This retrospective multicenter study examined VDZ effectiveness among anti-TNF naive patients, n=184.

  • For CD, 42/50 (82%) responded by week 14, and 32 (64%) were in clnical remission. At last followup (30-52 weeks), clinical remission was noted in 24/35 (69%)
  • For UC, 116/134 (79%) responded at week 14 and 53 (40%) were in clinical remission.  At last followup (30-52 weeks), 67% were in remission (69/103)

The authors conclude that VDZ is similarly efffective for anti-TNF naive CD and UC patients.

My take: These studies show that we still have a lot to learn about the effectiveness of VDZ as its use becomes more widespread.

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