NSAIDs and IBD

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While data has shown that nonsteroidal antiinflammatory drugs (NSAIDs) may worsen established IBD, whether these medications may serve as a trigger for IBD is less clear. One recent study indicates that NSAIDs may raise the risk of developing IBD (Ann Intern Med 2012; 156: 350-9).

This study examined the risk by using data from the Nurses Health Study which included 76,795 women.  Aspirin and NSAID use were self-reported.

Results:

  • “123 incident cases of CD and 117 cases of UC occurred over 18 years and 1,295,317 person-years of follow-up”
  • Frequent NSAIDs users (at least 15 days per month) had “increased risk for both CD (absolute difference in age-adjusted incidence, 6 cases per 100,000 person-years [95% CI, 0 to 13]; multivariate hazard ratio, 1.59 [CI, 0.99 to 2.56])”
  • And “UC (absolute difference, 7 cases per 100,000 person-years [CI, 1 to 12]; multivariate hazard ratio, 1.87 [CI, 1.16 to 2.99])”
  • There was no association with acetaminophen or aspirin within the same cohort.  This lessens the possibility of a false association; if subjects were treating GI symptoms, it is likely that an association would have been seen with all analgesics

The authors conclude that any absolute risk is low and therefore more important in understanding mechanism rather than in altering clinical use of these medications.

Link to abstract: Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn …

Additional NSAID references:

  • Gastroenterol 1966; 51: 430.  Sentinel article describing NSAID GI risk.
  • Gastroenterol 2008; 134: 1224.  Use of NSAIDs and risk prevention.
  • Clin Gastro & Hep 2007; 5: 1040. Long term effects of NSAIDs similar to COX-2 selective agents on small bowel mucosal damage (62% had abnormalities vs 50% of COX-2)
  • Clin Gastro & Hep 2006; 4: 1082 & 1090. Consensus on gastroprotection with NSAIDs.
  • Clin Gastro & Hep 2006; 4: 196.  NSAIDs worsen IBD.
  • Clin Gastro & Hep 2003; 1: 160.  Ileitis due to NSAIDs.

Why didn’t patient with documented reflux get better with PPI?

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There are numerous problems with pH studies; many of these problems have been alluded to in previous blog entries (see below).  Another problem is that these studies are not highly predictive of response to therapy (Gut 2012; 61: 501-506).

This French study from three centers examined 100 consecutive patients (58 females) with an average age of 50 years.  All patients had reflux symptoms, namely regurgitation and/or heartburn.  PPI dosage was not standardized and reflux symptoms were quantified with recall questionnaires.

The authors note that up to 40% of patients with reflux symptoms have inadequate symptom relief with a 4-week course of single dose proton pump inhibitor (PPI) therapy; the aim of their study was to investigate which factors on pH probe-impedance (pH-MII) would predict a response to therapy.

Definition: Nonresponders were patients who had more than 2 days of mild symptoms per week while receiving a standard or double dose of PPI treatment for 4 weeks

Results:

  • No reflux pattern on pH-MII was associated with a response to PPIs. Table 2 in the study looked at multiple factors including SI, SAP, time for acid exposure, and number of reflux events.
  • Lower BMI (≤ 25 kg/m-squared), non-erosive reflux, and normal pH study were associated with poor PPI response
  • Other factors associated with poor PPI response: female gender, irritable bowel syndrome (IBS), and functional dyspepsia.
  • Response rates: 58% of individuals with BMI >25, 71% with esophagitis, 23% with functional dyspepsia, 30% with IBS
  • Among responders, 77% were receiving a single dose PPI

Some of the poor response may be related to the study population.  Only 35% had abnormal acid exposure.  In total, 67% were determined to have abnormal pH studies, though this was due to a large fraction having a positive symptom-reflux association analysis.

However, this study population likely reflects a typical clinical group of patients diagnosed with GERD and demonstrates some of the shortcomings of pH-MII in clinical practice.  Even patients with abnormal pH-MII studies, the presence of functional dyspepsia and IBS were strongly associated with PPI failure.

Previous related blog entries:

HEROES trial

Impedance recommendations from PIG

Gastroesophageal Reflux: I know it when I see it

Treating reflux does not help asthma

Unexplained chest pain

Adding Methotrexate to anti-TNF therapy

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While new therapies are emerging for inflammatory bowel disease as noted in recent blog entries on Vedolizumab and Tofacitinib, many patients have refractory disease and require management with available treatments.  One strategy in this situation has been to add methotrexate (Inflamm Bowel Dis 2012; 18: 1488-92).

This case series from the Mayo clinic reported their experience with 14 pediatric Crohn’s patients (10 males) who had methotrexate added to anti-TNF therapy.

Clinical remission was achieved in 50% (PCDAI <15) within 6 weeks with methotrexate (dose: 15 mg/meter squared –average dose 17.5mg SC weekly).  All patients received folate supplementation (1 mg daily). In this study, the average duration of methotrexate use was only 8.2 months & average followup was only 10 months.

Discussion notes that prior to methotrexate all patients had active disease despite anti-TNF therapy & most had received thiopurines. Most patients tolerated methotrexate. Four patients had Clostridium difficile infection; two cases were de novo.  Even after treatment of the infection, patients with Clostridium difficile were refractory to methotrexate treatment.

Of the initial 14 patients, two patients had severe nausea; this resulted in medication discontinuation in one patient and dose reduction in another patient.  No liver or kidney toxicity was identified.

Patients who did not respond to methotrexate, subsequent care including the following: three had surgery, one received tacrolimus/corticosteroids, one received natalizumab, one received certolizumab, and one received adalimumab/corticosteroids (while awaiting screening for certolizumab).

A prospective study of methotrexate is needed to confirm the its effectiveness in refractory Crohn’s and to determine long-term safety and efficacy.

Patient information on methotrexate (from my office website):  Methotrexate

Related blog entries:

Drug levels for inflammatory bowel disease

Methotrexate and liver toxicity

Additional methotrexate references:

-IBD 2011; 17: 2521. Methotrexate therapy: ~25% remission at 1yr, 16% at 2yrs.. n=93.
-JPGN 2011;53: 389. n=64. Supports use of zofran for 1st few months to prevent nausea.
-JPGN 2010; 51: 714. Use of MTX after thiopurines. n=27. 48% in remission at 6 months.
-JPGN 2009; 48: 526. Use in pediatric CD, n=25. 64% response

Fontan and PLE

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In my practice, I am asked to give input on patients with Fontan procedure infrequently.  A few recent articles though are a good resource:

  • Nutr Clin Pract 2012; 27: 375-84
  • J Pediatr 2012;161:186-90

Both articles review the physiology and therapies available.  In essence, the Fontan operation establishes a passive connection between the systemic venous return and the pulmonary circulation.  When there are elevated inferior vena cava pressure, this can lead to hepatic dysfunction and protein-losing enteropathy.  The latter is related to engorged intestinal lymphatics, similar to that in congenital intestinal lymphangiectasia.  When lymphatic proteins leak, PLE only develops when the intestinal leak exceeds the patient’s ability to resynthesize lost proteins.

PLE presenting features: edema, diarrhea, bloating, pain, and pleural or pericardial effusions.  PLE places patient at risk for growth failure and associated problems. In more severe cases, hypocalcemia and infections due to lymphopenia can be present.

Potential treatments:

  • Agents that improve heart function -diuretics, pulmonary vasodilators (eg. sildenafil)
  • Corticosteroids including budesonide.  While improvement is common, hypoproteinemia returns after weaning of medication.  Systemic side effects occur even with budesonide.
  • Low molecular weight heparin.  Heparin likely helps by acting as a barrier to large molecules by improving the integrity of the basement membrane
  • Octreotide -has shown some effectiveness as an adjunct to other therapies in small studies
  • Albumin infusions
  • Diet: high protein (≥ 2 g/kg/day), low-fat (<25% of calories from fat), increase medium-chain triglycerides, & sodium-reduced
  • Surgical treatment (eg. atrial baffle fenestration) and cardiac transplantation

The second reference notes that many centers are delaying the Fontan procedure and accepting some degree of hypoxemia.  The problems with this approach include symptoms like headaches and decreased energy levels and the likelihood of developing pulmonary arteriovenous malformations.  Ultimately, the authors hypothesize that biomedical engineers may develop better solutions with miniaturized mechanical support devices to improve pulmonary blood flow.

Additional references:

  • Ann Thorac Surg 2010; 89: 837-42.  Budesonide for Fontan-associated PLE
  • Ann Thorac Surg 2011; 92: 1451-56.  Budesonide for Fontan-associated PLE
  • Congenit Heart Dis 2009; 4: 107-11.  Use of sildenafil for failing Fontan.

ELEVATE study

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Another clever acronym for the following:  Eltrombopag Evaluated for Its Ability to Overcome Thrombocyopenia and Enable Procedures (NEJM 2012; 367: 716-24).

Eltrombopag is an oral thrombopoietin-receptor agonist which is approved for use in chronic immune thrombocytopenia.

This double-blind, placebo-controlled trial evaluated whether eltrombopag increased platelet counts and reduced platelet transfusions in patients with chronic liver disease & platelet counts less than 50,000 per cubic millimeter.  145 patients received eltrombopag (75 mg once a day) and 147 received placebo.  Patients received therapy for 14 days. Elective procedures were scheduled no more than 5 days after the final dose of study medication (days 15 to 19).

Key findings:

  • Transfusions of platelets were reduced in the treatment group: 28% of patients compared with 81% in placebo group.
  • No differences in significant bleeding episodes noted.
  • Portal venous thrombosis was increased in treatment group with 6 patients compared with 1 patient in placebo group.

Study limitation: no standard practice with regard to use of platelet transfusions for thrombocytopenia (especially with platelet counts between 50,000-80,000)

Platelet transfusions can be problematic with cirrhosis.  Platelet transfusions have a short duration of efficacy, reactions to transfusions can occur, and multiple transfusions can result in antiplatelet antibodies. Nevertheless, the conclusions from this study: ‘until better identification of risk factors for the development of thrombosis…have been conducted, eltrombopag is not recommended as an alternative to platelet transfusion.’

TPN cycling

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A randomized prospective study of early parenteral nutrition cycling was not helpful in reducing parenteral nutrition associated cholestasis (PNAC): J Pediatr 2012; 161: 229-33.

This study enrolled preterm infants <1250 g in the first five postnatal days to either cycled (n=34) or continuous parenteral nutrition (n=36).  Cholestasis was defined as direct bilirubin >2 mg/dL. The study indicated that intralipid 20% was administered in all patients over 18 hours; the exact amount is not clear, though in the cycled group, patients received 3 g/kg/day on postnatal day 3.9 ± 2.6.  All patients received dextrose over 24 hours; only the amino acid (TrophAmine) infusion varied: 20 hours compared with 24 hours.

  • PNAC in each group was nearly identical, 32% vs 31% as were bilirubin and transaminase values.
  • While the study was randomized, the cycled group did have more frequent late-onset sepsis 22 (65%) compared with 14 (39%) which reached statistical significance.
  • In addition, a trend towards more frequent non-surgical NEC in cyclical group was noted as well: 6 (18%) compared with 3 (8%).
  • PNAC was associated with days until full enteral nutrition/duration of parenteral nutrition and bronchopulmonary dysplasia.

The higher incidence of late-onset sepsis could have occurred randomly and affected the results; alternatively, the higher rate could reflect an increased risk of sepsis due to doubling the frequency of central line access.

This study was  only powered to detect a 25% difference between the groups; the authors estimate that a study with 290 patients would be needed in each group to identify a reduction of 10% in the incidence of PNAC.  As such, this study leaves open the possibility that cycled parenteral nutrition may be helpful in a smaller percentage, particularly if efforts are made to eliminate central line infections.  More promising efforts to minimized PNAC are noted in previous blog entries:

PNAC, PNALD, and IFAC

Optimizing lipids to minimize cholestasis

More on PNAC

Four advances for intestinal failure

Electrons and Organic Food

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I still remember the Heisenberg uncertainty principle (Heisenberg states the uncertainty principle – PBS) from high school physics –thanks Mr. Pryor!  What quantum physicists don’t realize is that it is a leap of faith for anyone to believe in electrons much less to be concerned about measuring factors like speed or position.  I’ve never seen an electron but I’ve been convinced that they exist.

With organic foods, many people believe a health benefit exists, but does it and can it be proven?  A recent review weighs in (Ann Intern Med 2012; 157: 348-66) –thanks to Seth Marcus for pointing out this article.

This review from Stanford has been reported in multiple outlets and the soundbite is that organic foods are not better than conventional foods.  For example, the New York Times reports that the researchers “concluded that fruits and vegetables labeled organic were, on average, no more nutritious than their conventional counterparts, which tend to be far less expensive. Nor were they any less likely to be contaminated by dangerous bacteria like E. Coli.” Ultimately, “the researchers also found no obvious health advantages to organic meats.”

This is a vast oversimplification of this review.  So what did the researchers find and what were the limitations?

First –some background:

  • In 2010, U.S. sales of organic foods had increased to $26.7 billion; in contrast, only $3.6 billion was spent in 1997.
  • There are a number of different standards for organic foods, including U.S. Department of Agriculture (USDA), European Economic Community (EEC), and international federation of organic agriculture movement (IFOAM).
  • Typically organic foods are grown without synthetic pesticides or fertilizers or routine use of antibiotics/growth hormone.
  • Consumers often purchase organic foods due to concerns about effects of farming practices on environment, human health, animal welfare or perceptions of better taste.
  • Inclusion criteria for the cited reference allowed for 17 human studies and 223 nutrient/contamination studies of the initial 5908 potential relevant articles.

Key findings:

  • Conventional foods had 30% higher risk for pesticide contamination.
  • Conventional chicken and pork were more likely to have bacteria resistant to 3 or more antibiotics (33% risk difference).
  • Both organic and conventional products had frequent contamination with bacteria like Salmonella and Campylobacter.  Organic produce had higher risk for contamination with E. coli; this may have been due to some organic farms which used manure for fertilization.
  • There was not evidence that the organic foods were more nutritious.
  • Organic foods had higher levels of total phenols and ω-3 fatty acids.

Limitations:

  • No long-term studies of health outcomes have been performed.  The study with the longest duration included in this analysis was 2 years; the shortest was two days.
  • Variation in organic practices. Produce studies may not have reflected real-world organic practices.
  • Overall sample sizes were small (in total 13,806 human participants in 14 unique populations).
  • Reporting/publication bias.
  • Adherence with organic diets was varied; only 5 of the human studies evaluated participants who consumed a predominantly organic diet.

So, when one looks at this review, there are measurable differences in exposure to pesticides and antibiotic-resistant bacteria, despite variation in organic practices.  Specific nutrients are largely the same.  Whether any of these changes have a long-term health benefit is not known and would require an expensive long-term study to sort out.

 

One approach towards organic foods has been recommended by the Environmental Working Group.  They recommend “buying only organic when purchasing foods that contain the highest concentrations of pesticides, otherwise known as ‘the dirty dozen‘: peaches, strawberries, nectarines, apples, spinach, celery, pears, sweet bell peppers, cherries, potatoes, lettuce, and imported grapes” (Am J Clin Nutr 2010; 9 (suppl): 1499S-1505S).  This reference which discusses foods and potential hormonal effects on puberty goes on to state, “the biggest environmental exposure…is the ready availability of energy-dense foods” which contribute to obesity.

Related link:

Why are we seeing so many more cases

What do you know about the “exposome”?

Understanding IL28B

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Interleukin-28B (IL28B) has been a phenomenal discovery in the field of hepatitis C (HCV); yet, with the emergence of direct-acting antiviral (DAA) agents, its importance has been overshadowed.  While the long-term significance of IL28B is unclear, for now, it has significant clinical utility.  Three reviews/commentaries help elucidate its role:

▪                Hepatology 2012; 56: 361-66. IL 28B Genetics and Biology

▪                Hepatology 2012; 56: 367-372 Clinical Utility of IL28B

▪                Hepatology 2012; 56:  373-380 Relevance of IL28B in age of DAAs

Key points from these references:

African-Americans are less likely to respond to treatment with pegylated interferon (PEGIFN) (and ribavirin [RBV]) in large part due to a low frequency of favorable alleles (C/C genotype) to IL28B.

Predictors of response to treatment with PEGIFN/RBV:

▪                CC IL28B genotype: OR 5.9 (compared to non-CC genotype)

▪                HCV RNA level ≤600,000 IU/mL: OR 3.1 (compared to >600,000 IU/mL)

▪                Degree of fibrosis, metavir F0-2: OR 2.7 (compared with F3-F4)

▪                Rapid virological response: OR 9.1 (compared with non-RVR non CC genotype)

Overall CC genotype is associated with double the sustained virological response (SVR).

Vitamin D also plays an important role in innate immunity and deficiency is associated with lower SVR.

Algorithm for use of IL28B (applicable to patients ≥18 years):

▪                Consider obtaining IL28B in all genotype 1 patients:  

▪                If CC genotype and does not have risk factors for poor response (including cirrhosis, high viral load), then likely to treat with PEGIFN/RBV and monitor for RVR.  In patients without RVR, addition of DAA would be reasonable.

▪                If risk factors for poor response or if non-CC genotype (C/T or T/T), then consider use of DAA at onset of therapy

DAAs are expensive.  Boceprevir (BOC) costs $26,000 for 24 weeks & $48,000 for 44 weeks.  Telaprevir (TVR) costs $49,000 for 12 weeks.  These costs are in addition to costs for PEGIFN/RBV which is approximately $30,000.  The cost of testing IL28B status is approximately $300.

In patients with CC IL28B genotype, the main advantage of DAAs may be to shorten treatment course by increasing the likelihood of RVR; though with TVR, the SVR was improved even among CC genotype patients in the “ADVANCE” trial (90% compared with 64%).  In non-CC IL28B genotype, TVR or BOC is associated with > 2-fold increase in SVR.  The specific response rates for both TVR and BOC are available in these references.

Related blog entries

Pediatric HCV Guidelines

Increased ferritin predicts poor response in Hepatitis C

Unknown unknowns for Hepatitis C

HCV now more deadly than HIV

The cost of progress in treating Hepatitis C

Adalimumab for children with Crohn’s disease

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While adalimumab has been used in children with refractory Crohn’s disease, there has not been a lot of available data.  However, this situation has improved with the publication of the “IMAgINE 1” study (Hyams JS et al, Gastroenterology 2012; 143: 365-74).

This study enrolled 192 pediatric (6-17 yr-old) patients with moderate to severe Crohn’s disease; patients had PCDAI >30 and had failed conventional therapy with the exception of infliximab.  Approximately 45% in both groups had received prior treatment with infliximab.  The study started as an open-label induction followed by double-blind randomization into either a high-dose or low-dose maintenance phase.

Dosing:  For open label, patients >40 kg received 160 mg at week 0 and 80 mg at week 2.; patients <40 kg, received 80 mg at week 0 and 40 mg at week 2.

For maintenance, high dose was considered 40 mg every other week (eow) if >40 kg, and 20 mg eow if <40 kg.  Low dose was 20 mg and 10 mg respectively based on weight.

Results: 152 of 188 patients completed 26 week study period; 4 patients did not complete induction period.  At week 26, 63 patients (33.5%) were in clinical remission.  The high-dose remission response was 38.7% which was not statistically different from the 28.4% response in the low-dose group.

At week 52, there was a statistically improved response rate in the high-dose group 41.9% compared with low-dose group 28.4%; at the week 52 point, the remission rates were 33.3% compared with 23.2% respectively (p=0.1).  Among patients who were at least 13, it is noted that the overall CDAI clinical remission rate was 51% (week 26) and 36% (week 52) which are comparable to adult data from CHARM study.

Based on previous infliximab: Patients who had prior infliximab did not respond as favorably as infliximab-naive patients.  In the high dose group, the clinical remission at week 26 was 56.9% for infliximab-naive group compared to 16.7% for infliximab-experienced.  Similarly, the infliximab-naive response was higher, 68.6% compared with 47.6% for the infliximab-experienced.

Safety: “No new safety signals were detected.” Yet, 101 of 192 patients had adverse events during open label period, including 2 serious infections (which resolved & patients completed study).  Eight serious infections were noted during double-blind period.  Other safety problems included hepatic-related events in 9 of 188 patients, injection site reactions in 19 patients, hematologic adverse events in 8 patients, and 8 allergic reactions.  There were no reports of malignancy, congestive heart failure, lupus-like syndrome or demyelinating disease.

In both the high-dose and low-dose group, switching to weekly therapy instead of eow was allowed and commonly occurred: 48/95 in low-dose & 35/93 in high-dose.

Reasons for discontinuation: In both groups, drug discontinuation was frequent.  In the low-dose group, 37 patients stopped therapy.  In 18, this was due to lack of efficacy.  The other reasons included adverse effects in 10, protocol violation in 4, withdrew consent in 4, and lost to followup in 1.  In the high-dose group, 27  stopped therapy.  In 11, this was due to lack of efficacy; 12 had adverse effects, 2 withdrew consent, and 1 had protocol violation.

Another recent article (Inflamm Bowel Dis 2012; 18: 685-90) indicates that the annual risk of loss of response to adalimumab was 18% per year of followup.  This study involved 380 CD patients with an average age of 38 years.  This study also showed that there was a significant difference between patients naive to anti-TNF therapy and those who had prior anti-TNF therapy:  8% loss of response per year of followup compared with 22% respectively.

Related blog entries:

TNF-α antagonists and infections

CHOOSE TNF TRIAL

Disease modifying treatment in IBD

Only one chance to make first impression

TNF antagonists and UC

Adalimumab references:

  • -Gut 2011:  Gut doi:10.1136/gut.2010.221127. Use in induction of remission in UC. Reinisch W, et al. Adalimumab for induction of clinical remission in … – Gut – BMJ
  • -Aliment Pharmacol Ther 2010; 32: 1228-39. CHOICE trial. adalimumab effective in pts failing prior IFX.
  • -Gastroenterol 2009; 137: 1628. n=168.  71% & 67% of pts responded by weeks 4 & 12.  61% demonstrated sustained benefit. (in IFX failure pts). Of 156 pts, 65% needed to step up to 40mg weekly and 60 eventually stopped adalimumab due to loss of response.  Lower trough levels associated with loss of effectiveness & often with antibodies to adalimumab (present in 9.2% of pts).
  • -IBD 2011; 17: 2512.  n=50.  62% of pts develop skin reactions: eczema, acne-like dermatitis, psoriasis-like (6 of 50).  Adalimumab d/c’d in 22%.  Message -see dermatologist
  • -Lofberg et al. Am J Gastro 2008; 103: S418 (abstract 1069) Care study. -n=945. Humira at week 20 -remissions in 52% of pts naive to biologics, in 46% who prev responded to IFX & became intolerant, in 40% who prev responded to IFX and lost response, and 36% of pts with primary non-response to IFX.
  • -IBD 2008; 14: S1 Abrstarct 0002. Humira in TNF-naive patients with Crohn’s disease. Decreases hospitalizations. (12 month: 12.7% vs 20.3% in placebo group) Adult dosing: Induction 160mg, then 80mg in 2 weeks, then 40mg every 2 weeks.
  • -IBD 2008; 14: 1683. Response to adalimumab in 10 children.
  • -Gastro 2008; 135: 1493. n=778. mod-to severe Crohn had less hospitalizations (decreased ~60%) and surgery if Rx’d w Humira. 40mg eo week or qweek post 80/40 induction
  • -NEJM 2008; 359: 810. Use in pediatric JRA -helpful.
  • -JPGN 2008; 47: 19. n=15 pediatric patients. Complete or partial response in 64%.
  • -Gastro 2007; 132: 52. CHARM Trial. n=778. 40mg weekly c 47% response at week 26 (17% placebo) & 41% @ week 52 (12% placebo); works nearly as well in pts c prev inliximab as naive pts. Rapid onset ~c/in 2 weeks
  • -Clin Gastro & Hep 2006; 4: 1199-1213. Excellent review. Suggested dosing: 20mg every other week if 20-25kg, 25mg every other week if 25-30kg, 30mg every other week if 30-40kg, 35mg every other week if 40-55kg,  40mg every other week if >55kg, and increase to weekly dosing if needed
  • -JPGN 2008; 46: 1208, 226. pediatric case report and review of CHARM
  • -Gastro 2006; 130: 323-333. CLASSIC-I Trial, n=299. 36% 4-week response to 160mg/80mg week 0/subsequent week 2 (vs. 12% of placebo) All pts naive to anti-TNF Rx.

Adalimumab Injection Pain

  • –Suggestions from GI bulletin board. 1)you let the Humira Pen sit out for about 30 minutes prior to administering the medication, so that it appears clear and not foggy, that it greatly reduces pain at the site. 2) the pain disappeared after adding bicarbonate to the Humira. By trial and error, our nurse found that 0.15cc of bicarbonate is the minimum amount that yields a good effect.
  • -Lidocaine with adalimumab. Abstract reference: AF Ayala, Rosanne S.Groh, Brandt P.Robbins, Lisa M.Scalzi, Lizabeth Bingham, C. April TI The addition of injectable lidocaine to adalimumab results in decreased injection site pain and increased acceptance of therapy. 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals. CY OCT 24-29, 2008 CL San Francisco, CA. They used 0.2 ml 1% lidocaine into prefilled adalimumab syringe. We’ve tried this with a few patients and it seems to work well.
  • -Pt developed a “shot blocker” that is a bristle brush with a central hole for the syringe. The brush diffuses the pain from the Humira injection. Click the link below for a youtube video he created.
  • -http://www.youtube.com/watch?v=nfL95YRlTjY

Salt for POTS –who benefits?

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Individuals with postural orthostatic tachycardia syndrome (POTS) who have low baseline urinary sodium excretion (<124 mmol/24 hours) were more likely to benefit from sodium supplementation (J Pediatr 2012; 161: 281-4). In this group, “as much as 90% of patients” will improve with salt supplements.

This study from China examined the effects of sodium supplementation in 30 children (20 females, 10 males) as well as in 10 control patients to identify factors which related to therapeutic response.  Criteria for POTS included orthostatic intolerance (without orthostatic hypotension –blood pressure drop >20/10 mm Hg) accompanied by a heart rate increase of >30/min within the first 10 minutes of standing.

Despite normal serum sodium, POTS cohort had baseline 24-hr sodium excretion of 117 ± 59 compared with control of 194 ± 91.  POTS sodium-responders were similar in all aspects at baseline except for lower sodium excretion: 85 ± 35 compared to 150 ± 51 for POTS sodium-nonresponders.

The discussion reviews the theoretical reasons for POTS response to sodium (e.g.. ‘relative hypovolemia’) and points out that there are several subtypes, including ‘hypovolemic,’ hyper-adrenergic,’ and ‘autoimmune.’ Salt supplementation which has been shown to be effective only in the pediatric population targets the hypovolemic subset.

Limitations:

  • Small sample size
  • Lower sodium excreters had more symptoms at baseline & therefore may have led to bias as well

Additional references:

  • -J Pediatr 2011; 158: 20 (pg 4 editorial). n=53. GI pain in 75%, nausea/vomiting in large fraction, sleeping problems in 98%, headache, syncope, urinary symptoms. May have poor stomach emptying due to autonomic dysfunction
  • -J Pediatr Gastroenterol Nutr. 2010 Sep;51(3):314-8. Gisela Chelimsky  “Gastric Electrical Activity Becomes Abnormal in the Upright Position in Patients With Postural Tachycardia Syndrome”
  • -J Pediatr 2011; 158: 499. Orthostatic hypotension can be treated physically: gripping hands for 15 secs before rising, lower body muscle contraction (eg pumping calf muscles/tensing legs), squatting…