NEJM: Analysis of the Graham-Cassidy Plan

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. 

 

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

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 AbstractPrediction 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)

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)

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.

Outcomes of Children Whose Mothers Have Inflammatory Bowel Disease

A recent study (LR Jolving et al. Inflamm Bowel Dis 2017; 23: 1440-46) used a nationwide (Denmark) register-based cohort to examine the health outcomes of children whose mothers have inflammatory bowel disease (IBD).  This cohort of 9238 children were compared with nearly 1.4 million children born to women without IBD. Median follow-up time was 9.7 years of the children whose mothers had IBD.

Key findings:

  • Hazard ratio for developing IBD in the offspring was 4.63 if maternal ulcerative colitis
  • Hazard ratio for developing IBD in the offspring was 7.70 if maternal Crohn’s disease
  • “Our data otherwise do not provide evidence for an increased risk of any of the other examined diseases in the offspring.” This included diabetes mellitus, thyroid diseases, rheumatoid arthritis, epilepsy, chronic lung disease, mood disorders, schizophrenia, epilepsy, and anxiety disorders.

Raw numbers for developing IBD:

My take: This study documents the expected finding of an increased risk of IBD among the offspring of women with IBD. No other chronic diseases were increased in this study.

Briefly noted: SM Yoon et al. Inflamm Bowel Dis 2017; 23: 1382-93.  This retrospective registry study included the following:

  • 314 subjects with Crohn’s disease (CD) who were primary nonresponders, and 179 with CD who were secondary nonresponders
  • 145 subjects with ulcerative colitis (UC) who were primary nonresponders and 74 with UC who were secondary nonresponders

Key findings: “Colonic involvement (OR 8.0) and anti-TNF monotherapy (OR 4.9) were associated with primary nonresponse to anti-TNF agents in CD.” Higher ANCA levels in UC (HR 1.6) were associated with time to loss of response to anti-TNF agents.

 

Combination Therapy with Adalimumab -Is it Helpful?

A recent study (JM Chalbhoub et al. Inflamm Bowel Dis 2017; 23: 1316-27) performed a systematic review and meta-analysis to examine the effectiveness of Adalimumab (ADA) combination therapy compared with monotherapy.  With infliximab (IFX), the SONIC study, showed that combination therapy with an immunomodulator (IMM) (azathioprine) improved response; combination therapy resulted in reduced immunogenicity, lower rates of infusion reactions, and higher IFX levels.

With the advent of widespread use of therapeutic drug monitoring, some have questioned the need for combination therapy with IFX.  The need for combination therapy for ADA is also a matter of debate.  ADA has less immunogenicity than IFX and it is unclear if combination therapy will improve outcomes. There have been conflicting studies regarding combination therapy with ADA, prompting the current meta-analysis.

The authors identified 24 articles for inclusion from an initial pool of 1194. Key findings:

  • No significant difference between combination therapy and monotherapy was noted for induction of remission (OR 0.86) or response (OR 1.01). The induction of remission is based on data from 3096 patients (1400 on combination treatment).
  • No difference was noted for maintenance of remission (OR 0.97) or response (OR 0.91). The maintenance of remission is based on data from 1885 patients (859 on combination treatment).
  • Patients receiving combination therapy had lower odds of developing antidrug antibodies (OR 0.24)
  • Subgroup analysis in anti-TNF experienced patients showed improved successful induction of remission (OR 1.26) but also more frequent opportunistic infections (OR 2.44)

Overall, the authors conclude that “combination of ADA and immunomodulators does not seem superior to ADA monotherapy for induction and maintenance of remission and response to Crohn’s disease.” They do comment on the recent DIAMOND study which was a randomized open-label top-down strategy trial in anti-TNF-naive and IMM-naïve patients.  While no overall advantage of combination therapy was evident, better endoscopic response (84% vs. 64% with monotherapy) was seen at 26 weeks (but not at 52 weeks).

This study has several limitations.  Overall, there were a small number of randomized trials and the trials had significant heterogeneity.

My take (borrowed from authors): “It is unclear whether the addition of IMM impacts the efficacy of a less immunogenic anti-TNF biologic such as ADA in CD.” Though, in the subgroup of anti-TNF exposed patients, “combination therapy was associated with higher odds of induction of remission.”

Related blog posts:

An Allergy-Immunology View of GI Diseases

Recently, one of our allergy-immunology colleagues, Dr. Kiran Patel, from Emory presented an update on GI Diseases from an allergist viewpoint at one of our GI clinical education meetings. With his permission, many of the slides are noted below.  The slides present a good deal of information, though a lot of nuance and further details were provided by Dr. Patel.

Next few slides discuss typical GI food allergies.  It is not surprising that a lot of allergies manifest with GI symptoms given the amount of immune cells in the intestines and frequent interactions with foods and antigens.

This next slide points out that four of the most common food allergens (cow’s milk, egg, soy, and wheat) are frequently outgrown, whereas with peanuts, tree nuts, fish, and shellfish, it is uncommon to outgrow these allergies..

The next slide discusses potential evaluation.  While the slide states that the positive predictive value of skin prick tests and serum-based IgE tests may be as high as 50%; in fact, when broad panels of allergy tests are ordered, the positive predictive value can be quite low.

Related blog posts:

Dr. Patel did discuss the LEAP study and the LEAP-ON study which overall indicate that early antigen introduction is likely to reduce food allergies. Related blog posts:

 

The next few slides review Food Protein-Induced Enterocolitis Syndrome. Related blog posts:

The next few slides discuss eosinophilic esophagitis (EoE).  Allergy testing has not been very helpful in most patients with EoE. Related blog posts:

The last part of Dr. Patel’s talk focused on GI disease (eg. inflammatory bowel disease presentation) of primary immune deficiencies.  In the bottom slide, the diseases that often present with GI symptoms are boxed.

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.