Biosimilars: “The Horse is Out of the Barn”

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A recent study (J Sieczkowska-Golub et al. JPGN 2017; 65: 285-88) reports on 36 pediatric patients who received CT-P13, an infliximab biosimilar.  Key findings:

  • 34 of 36 (94.4%) completed induction therapy
  • Clinical response based on pCDAI was noted in 31 of 36 (86%)
  • Clinical remission based on pCDAI was noted in 24 of 36 (67%)

The authors concluded that the induction was effective and similar to the reference infliximab.

In the accompanying editorial, Dr. de Ridder and Dr. Winter make some crucial observations:

  • “Although the study…is important, the number of subjects in this study are low and follow-up is short (14 weeks).”
  • “It is still a large step from adults to children.” Children may have important differences in IBD pathogenesis and pharmocokinetics may not be the same as in adults.
  • The studies supporting CT-P13 (Planetas, Planetra, and NOR-SWITCH) were studies of adult patients.
  • “The data in children are scarce.” However, “the horse has already left the barn. In many European countries both naive pediatric patients with IBD and patients who have switched from the originator are treated with CT-P13.”
  • While “caution is still needed,” the lower costs of CT-P13 will “lead to wider availability.”

My take: We still have a lot to learn.  Until more studies are available, switching stable patients could increase risk of losing response.

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Eiffel Tower

FDA Warning for Obeticholic Acid

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Obeticholic acid was approved last year as a treatment for primary biliary cholangitis (PBC). Now (9/21/17), the FDA warns of 19 deaths associated with Obeticholic Acid, particularly when the medication has been used at higher than recommended dosing.

Link: FDA Warning on Obeticholic Acid

An excerpt:

Nineteen cases of death were identified, of which eight provided information about the patient’s cause of death. The cause of death was reported to be worsening of PBC disease in seven cases, with cardiovascular disease cited in the other case. Seven of these eight cases described patients with moderate to severe decreased liver function who received Ocaliva 5 mg daily, instead of a dose no greater than 10 mg twice weekly as recommended in the label prescribing information for patients with this extent of decreased liver function.

NEJM: Analysis of the Graham-Cassidy Plan

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NEJM: The Graham-Cassidy Plan -The Most Harmful ACA-Repeal Bill Yet

An excerpt:

The Graham–Cassidy bill would begin by repealing the individual and employer mandates retroactive to 2016. The Congressional Budget Office (CBO) previously estimated that repeal of the individual and employer mandates would immediately increase the number of uninsured Americans by 15 million or more and increase individual market insurance premiums by 20%…

The Graham–Cassidy formula would shift money from states that expanded Medicaid coverage under the ACA or increased take-up among previously eligible groups to those that did not. It would also shift money from high-cost to low-cost areas…

the bill would permit states to waive the ACA requirements that insurance sold in the individual market cover essential health benefits and that insurers not vary premiums on the basis of health status, thereby restoring the ability of insurers to engage in “medical underwriting” and effectively deny coverage or limit services on the basis of preexisting health condition..

All told, we estimate that under Graham–Cassidy, an additional 21 million people would be without insurance coverage in 2020 and later years, and this figure may be conservative..

It replaces effective coverage programs with a block grant that is inadequate in the aggregate and blind to variations in local costs, shifting considerable risk onto states. It would slash the program that provides health insurance coverage for the poor. 

 

CCFA: Updates in Inflammatory Bowel Disease 2017 (part 3)

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More from our recent CCFA Conference.  My notes may include some errors in transcription and errors of omission.

Subra Kugasthasan -RISK Updates

Dr. Kugasthasan’s lecture was excellent.  He reviewed the typical clinical course of Crohn’s disease; in most patients, it has a remitting and relapsing course.  The goal of the CCFA-sponsored RISK study was to determine how early approaches to treatment affect long-term outcomes.  There is likely a window of opportunity to more favorably affect natural history of the disease. In addition, the goal is to determine whether there are predictive markers of severe disease course.  This prospective study analyzed 913 patients.  In this cohort, 835 remained with B1 (inflammatory) phenotype and 90 developed either B2 (stricturing) phenotype or B3 (penetrating) phenotype.

RISK Study Abstract: Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study (S Kugathasan et al. Lancet 2017; 389: 17108. DOI: http://dx.doi.org/10.1016/S0140-6736(17)30317-3)

Key findings:

  • Early TNF therapy reduced the likelihood of penetrating (B3) but not stricturing (B2) disease
  • Based on analysis of genetic expression at baseline, individuals who are likely to develop B2 or B3 disease can be identified. This assay may be available clinically in a few years

Jahnavi Srinivasan -Multi-Disciplinary Approach to IBD A Surgical Perspective

  • Teeuwen PH et al study spans a long period and there have been many changes since that time. The study’s 9% 30-day mortality rate is very high (current Whipple 30-day mortality ~2%)
  • 3-stage surgery most common now for ulcerative colitis due to sicker patients who now need operation
  • Harder to differentiate UC and CD
  • Try to get patients off steroids; this is a key factor in surgical complications. Nutritional support may be helpful though some effects may be mediated by helping with steroid tapering

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and changes in diet 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.

CCFA: Updates in Inflammatory Bowel Disease 2017 (part 2)

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Douglas Wolf -New Treatments and New Strategies

  • More proactive approach is recommended; this leads to less surgery, less hospitalization, and less antibodies to infliximab
  • Risk assessment should guide treatment; higher risk indicates a need for more aggressive therapy
  • Higher doses of anti-TNFs appropriate in some cases (eg weekly Humira)
  • For distal colitis/proctitis, budesonide foam is an alternative to cortifoam
  • Azathioprine monotherapy has a low response rate
  • Combination therapy may not be needed if good IFX levels obtained.  Though, it is possible that development of antibodies precludes achieving good levels; thus, combination therapy may increase likelihood of good levels by reducing antibody formation, particularly earlier in course
  • Vedolizumab can be shortened to q4weeks if not improving.
  • CALM study: symptom based management compared to management based treat-to-target relying on CRP, and calprotectin. Improved outcomes with treatment based on CRP, calprotectin in addition to symptoms.
  • Tofacitinib –will be available in 2018 for ulcerative colitis

Chiristina Ha -Treatment Strategies in the Elderly

Dr. Ha referenced Dr. Sandborn who recently stated that combination therapy should be first-line therapy in moderate-to-severe disease –though this may be different in elderly patients.

  • Older age –increases mortality risk
  • Immunosenescence -relative immunodeficiency state associated with aging
  • Pharmokinetic changes with aging
  • Increased susceptibility to drug toxicity (eg. Renal, hepatic)
  • Older patients usually excluded from therapeutic trials
  • Polypharmacy is more common

Treatment:

  • Frequent strategy in elderly has been using 5-ASAs and steroids, even in moderate-to-severe disease. This has been due to increased fear of adverse events with IMM and anti-TNFs.  However, using data from rheumatoid arthritis, older patients’ biggest risk is steroids.
  • Thiopurines have unfavorable risk profile in the elderly.
  • Anti-TNFs are not as effective in the elderly
  • Preliminary data on vedolizumab -very limited data, may work better in older patients
  • Most common infections by be reduced considerably by immunizations. (eg.  ,bacterial pneumonia, herpes zoster)
  • Correct anemia, nutritional deficiencies

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and changes in diet 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.

CCFA: Updates in Inflammatory Bowel Disease 2017 (part 1)

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Our local CCFA chapter provided a useful physician CME meeting.  The following are my notes/picutres. My notes may include some errors in transcription and errors of omission.

Nancy McGreal  -Complementary Therapies in IBD

Key points:

  1. Curcumin and VSL#3 are likely helpful
  2. Most complementary and alternative medicine (CAM) therapies are not inherently dangerous, but most are unproven
  3. Biggest risks: Nonadherence rates are increased in patient taking CAM.
  4. Despite the low overall risk of most CAM treatments, Dr. McGreal cautioned against the following:
    1. Cannabis is NOT recommended due to neurocognitive effects. It may mask active disease.
    2. FMT investigational. There are unknown risks but FMT could cause metabolic problems. Donor selection is important and we still have a lot to learn.

This final slide is from CCFA about how to order more patient information brochures.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and changes in diet 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.

Physician Burnout Spreading (Part 2)

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A recent article (JC Anderson et al. Am J Gastroenterol 2017; 112:1356–1359; doi: 10.1038/ajg.2017.251; published online 8 August 2017) also addresses the topic of physician burnout with a focus on gastroenterology, link: Strategies to Combat Physician Burnout

Excerpts:

  • Physician burnout has reached epidemic proportions, with 54.4% of physicians reporting at least one burnout symptom in 2014, an increase from 45.5% 3 years earlier
  • A Medscape survey in 2016 showed a burnout rate among gastroenterologists of 49%, up from 41% the year before
  • Key drivers of burnout are excessive workload, an inefficient environment and
    inadequate support, problems with work life integration, loss of value and meaning in work, and the loss of autonomy, flexibility, and control in work 
    The cost of burnout is high, as these physicians are more likely to leave medicine, retire early, make more medical errors, and have lower patient satisfaction scores

Combating Physician Burnout:

  • Leadership : Having good leaders affects the well-being and satisfaction of physicians in health care organizations
  • Reducing Administrative tasks -scribes, mid-level providers 
  • Control over workflow and work hours
  • “Peer support is crucial, nothing else can replace it.”
  • “Physicians who spend at least 20% of their total effort in an activity that they find most meaningful are at a lower risk for burnout”
  • Self-care: Stress management and mindfulness can reduce burnout

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Physician Burnout Spreading (Part 1)

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Last week, I went to our integrated health care network meeting.  Among the topics was physician burnout.  Lately, this is a “hot” topic with a lot of publicity regarding this increasingly-common problem.

At our meeting, some of the keep points -noted below & in the slides that follow:

  • Physician burnout rate is increasing based on most recent studies
  • Many physicians, 42%, would not choose medicine as their career today
  • Manifestations of burnout include “compassion” fatigue

Physicians may be more at risk for burnout due to the following:

  • Frequent personality characteristics: workaholics, accustomed to delayed gratification
  • Practice aspects: long hours, huge responsibilities

How to Prevent Burnout:

  • Lower stress –recharge with outside activities: hobbies, excursions, charitable work, physical activities, and emotional/spiritual
  • Resources: Stop Physician Burnout, Burnout Prevention Matrix  both by  Dike Drummond

 

Related blog post: Quality Care = Work Satisfaction for Physicians

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Eight Week Pangenomic HCV Treatment Approved

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FDA Announcement Aug 3, 2017: FDA approves Mavyret for Hepatitis C

An excerpt:

The U.S. Food and Drug Administration today approved Mavyret (glecaprevir and pibrentasvir) to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. Mavyret is also approved for adult patients with HCV genotype 1 infection who have been previously treated with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor but not both. 

Mavyret is the first treatment of eight weeks duration approved for all HCV genotypes 1-6 in adult patients without cirrhosis who have not been previously treated. Standard treatment length was previously 12 weeks or more.

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Overtreatment –Physician Perspective

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From NY Times: Overtreatment is Common, Doctors Say

An excerpt:

Researchers surveyed 2,106 physicians in various specialties regarding their beliefs about unnecessary medical care. On average, the doctors believed that 20.6 percent of all medical care was unnecessary, including 22 percent of prescriptions, 24.9 percent of tests and 11.1 percent of procedures. The study is in PLOS One.

Reasons for overtreatment that were cited:

  • Fear of malpractice “that fear is probably exaggerated, the authors say”
  • Patient demand
  • Financial incentive

My take: It takes more time explaining why a test/medicine/procedure is a waste of time than to order it; even then, many patients/families are unhappy if the physician does not order the test/medicine/procedure that they think is necessary.  Changing this dynamic is not easy.

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