Tag Archives: infliximab

Liver Injury from Anti-TNF Agents

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While anti-TNF agents have been associated with drug-induced liver injury (DILI), it has been difficult to get a handle on how much importance to place on this.  A recent study provides more data and some reassurance (Clin Gastroenterol Hepatol 2013; 11: 558-64).

The authors searched the U.S. DILI Network database from 2003 to 2011 and describe 6 cases of anti-TNF DILI; in addition, they searched PubMed for articles related to anti-TNF agent associated hepatotoxicity and identified an additional 28 cases. Other causes of liver disease were excluded in these patients, including reactivation of hepatitis B, and acute viral hepatitis (eg. hepatitis C, hepatitis E).

Results of anti-TNF hepatotoxicity:

  • 26 cases due to infliximab, 4 cases due to etanercept, and 4 due to adalimumab.
  • Based on scoring system, the anti-TNF agent was considered a definite cause of DILI in 1 (3%), very likely in 21 (62%) and probable in 12 (35%).
  • Median latency (duration of therapy before onset of DILI) was 13 weeks with a range of 2-104 weeks.
  • 22 (67%) had positive anti-nuclear and/or smooth muscle antibodies.  15 of 17 of these patients had liver biopsy features consistent with autoimmunity.
  • Among those 22 with autoimmune features, there was a higher peak alanine aminotransferase compared with the 12 without these features (784 vs 528 U/L)
  • Favorable outcome: all but one patient improved after discontinuation of the implicated drug; 12 received corticosteroids. One patient with underlying cirrhosis underwent liver transplantation after infliximab-induced liver injury.

While the authors note the potential for a class effect of anti-TNF agents, in studies from patients with psoriasis, there was a lack of cross-toxicity between etanercept and infliximab.

Take-home messages:

The risk of hepatocellular injury from anti-TNF agents is very low.  DILI due to anti-TNFs often have autoimmune features. The prognosis is favorable, and alternative anti-TNFs can be given after resolution.

Related blog links:

“Family Feud” for Pediatric Crohn’s Abscess Management

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Initially, this blog entry was titled “What is the best way to manage an intra-abdominal abscess in pediatric Crohn’s disease?”  My answer was simple: it depends on who you ask (Inflamm Bowel Dis 2013; 818-25).  As I thought about this study, the responses reminded me of “Family Feud” minus Richard Dawson.

This survey examined the responses of NASPGHAN members.  Of the initial 1608 emails which were delivered, 248 fully completed surveys.  25% of respondents were in practice for >20 years and 26% treated >50 patients with Crohn’s disease (CD). 87% of respondents were from U.S.

  • What is the best way to image initially?  52% recommended CT scan, 26% MRI, and 21% ultrasound.
  • What is the best modality for followup imaging? 47% ultrasound, 33% MRI, and 13% CT
  • Antibiotics or drainage for abscess <2 cm? 61% recommended antibiotics; 51% would treat for 3-4 weeks, whereas 19% for 1-2 weeks.
  • Antibiotics or drainage for abscess >2 cm? 28% would attempt antibiotics alone
  • When is surgery indicated? 75% said only in select cases after completing antibiotics and interventional radiology drainage.
  • Anti-TNFα therapy?  The survey also questioned the shortest preoperative interval one would prescribe anti-TNFα therapy.  The results ranged from 12% for <1 week to 45% who would not give anti-TNFα therapy at all.

The authors note that there is “a paucity of research and practice guidelines for the optimal management of children with intra-abdominal abscess.”  There were no trends in management identified based on practitioner level of experience.  Some answers to the questions are alluded to by the authors but not expressed definitively. For example, “several studies have reported a lack of association between infliximab and an increased rate of postoperative complications.” “Most infections that occur while on anti-TNFα therapy tend to be opportunistic, not bacterial.”

The study’s conclusions are limited by the low participation rate.  In addition, when physicians are confronted with a specific situation, their response in practice may be different than in a theoretical scenario.  However, it appears that the answers to these important questions are closer to guesses on a game show rather than best care.  More research and collaboration is needed to reduce this highly variable care and determine the most effective approach.

Related blog entries:

Don’t Fix What’s Not Broken

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A recent study provides information about elective switching from infliximab (IFX) to adalimumab (ADA) in stable Crohn’s disease (CD) (Inflamm Bowel Dis 2013; 19: 761-66).  As a practical matter, patients and families inquire about switching therapy due to potential convenience and flexibility.  Thus far, there is little data to guide clinicians.  As such, the authors explored this question by designing an open-label study which would allow enrollment of any patients who had stable disease for >6 months (Harvey-Bradshaw Index ≤ 8) on IFX therapy.

In total, 29 patients with CD were enrolled with an average age of 39.  Twelve had previous resections.

Key results:

  • 21 patients (72%) were able to remain on ADA at 54 weeks.  8 patients discontinued ADA due to disease activity (n=3), side effects (n=4), or other symptoms (n=1).
  • 4 patients were restarted on IFX therapy; 1 required dose intensification.
  • At 54 weeks, 13 patients indicated a preference for IFX due to efficacy (n=9) or safety profile (n=4).  12 patients indicated a preference for ADA.  4 patients had no preference.

The authors state that a recommendation to avoid elective switching.  In their study, 28% were not able to be maintained on ADA therapy, more patients preferred IFX after experiencing both therapies, and switching back to IFX has been associated (in some) with reduced efficacy.  The main concern with an elective switch is the potential loss of response with very limited therapeutic alternatives.

The authors note that their study showed better results with an elective change than a previous study (the SWITCH trial, n=73).  In the SWITCH trial, “elective switch from IFX to ADA in patients with stable CD led to 47% of patients requiring dose intensification or interruption of treatment” in the ADA arm compared with 16% of patients who continued IFX therapy.  (Adalimumab in Crohn’s Disease Controlled by Infliximab)

The better outcomes in the current trial may have been due to selection of patients with milder disease and the more frequent use of concomitant immunosuppression.  In the current trial, 52% had concomitant immunosuppression (48% thiopurine, 4% methotrexate); in contrast, only 17% received concomitant immunosuppression in the SWITCH trial.  Another important difference was that the patients in the current trial received 160-80 loading doses rather than 80-40 induction.  Also, the trial designs were different.  The current trial enrolled patients without randomization; in contrast, the SWITCH trial randomized some patients to continue IFX and others to change to ADA therapy.

Related reference:

  • -Gut 2012; 61: 229-34. SWITCH trial.

Related blog references:

CCFA IBD Update -Conference Notes (part 2)

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As noted in previous blog post, I wanted to share some notes from recent Atlanta CCFA talk.

The fourth lecture by Jeffry Katz discussed optimizing biologic therapy.  Overall this was an excellent review.  He discussed his general preference for combination therapy since the publication of the SONIC study. Also, he highlighted a smaller study that showed better efficacy with combination therapy in ulcerative colitis as well (DDW 2011, Abstract #835).

With regard to withdrawal of therapy when doing well on combination treatment, he indicated that he sometimes reduces (or stops) dosage of immunomodulator after 1 year but tries to avoid stopping anti-TNF agents.  Relapse rates after stopping infliximab in Crohn’s disease are approximately 50% at 1 year and 75% at 5 years.

His talk reviewed antibodies to infliximab and low therapeutic levels. This has been discussed on this blog previously:

He reviewed risks of the IBD medications.  With regard to psoriasis reactions, he stated that developing skin lesions occur in about 5% and this necessitates drug withdrawal in 1%.  As these skin reactions are often a ‘class effect,’ use of an alternative may be needed.  He stated that he had used ustekinumab in this setting (“but this entails a fight with the insurance company”).

The 5th talk by Doug Wolf reviewed pregnancy in IBD.  Much of the information has also been discussed in this blog recently: Anti-TNFs and Pregnancy | gutsandgrowth

His key points:

  • Probably stop infliximab at gestational week 32
  • Likely give adalimumab up until week 34-36
  • If patient in remission, consider stopping stopping drugs earlier
  • In PIANO registry (n=1000), use of anti-TNFs and immunomodulators was not associated with any complication, including prematurity, spontaneous abortion, intrauterine growth retardation or specific birth defects.  However, there was a significant increase in infant infections up to 12 months of life in the combination therapy group.
  • No live virus vaccines (eg. rotavirus) for first 6 months for infants exposed to infliximab

The last talk that I attended was a pediatric case presentation from Cary Sauer. He presented a teenage boy who had mild disease based on bloodwork and endoscopy who had more severe and extensive disease on magnetic resonance enterography (MRE) (More imaging needed? | gutsandgrowth) and video capsule endoscopy.  He argued that small bowel assessment is worthwhile in every patient at the time of diagnosis as more severe findings could influence the choice to start with top-down therapy.

The final aspect worth mentioning were some of the patient-related information:

1. A pediatric, adolescent, and parent support group will have its first meeting April 23rd 6-7:30 pm at Scottish Rite Children’s Hospital (Main auditorium).  Followup meetings are scheduled for August 27, and October 22. All meetings are free.  Contact CCFA mball@ccfa.org or 646-623-4869 (cell) for more information.

2. CCFA also has “Power of Two.”  This contacts patients/parents with peer mentors.  Interested patients can contact mball@ccfa.org or 404-982-0616.

Anti-TNFs and Pregnancy

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While pregnancy does not occur commonly while patients are in a pediatric gastroenterology practice, the possibility of becoming pregnant certainly influences our choice of medications.  With inflammatory bowel disease (IBD), I rarely recommend methotrexate in young women due to its teratogenicity.  With regard to the anti-TNF agents, there is less data available.   Two recent studies add some insight into this issue.

The first study ((Clin Gastroenterol Hepatol 2013; 11: 318-21) followed 31 pregnancies in 28 women with IBD (2006-2011).  18 patients received infliximab (IFX) and 13 adalimumab (ADA).  Most were receiving lower doses; only one IFX patient was receiving 10 mg/kg/dose and only two ADA patients were receiving weekly dosing.  Levels of anti-TNF agents were measured from cord blood from 18 newborns (12  IFX, 6 ADA).

Results:

  • 28 live births.  3 miscarriages (1 IFX, 2 ADA).  No congenital malformations were noted.
  • Mean cord IFX level was 6.4 mcg/mL.  A level of 2.8 mcg/mL was noted in the early discontinuation group –stopping 10 weeks prior to delivery .
  • Mean ADA level was 1.7 mcg/mL in five infants.  One infant had an undetectable level. All mothers had stopped ADA at gestational week 22.

In the second study (Clin Gastroenterol Hepat 2013; 11: 286-92) there were 31 pregnant patients. Anti-TNF treatment: Certolizumab (CZP) (n=10), IFX (n=11), ADA (n=10).  Serum levels were measured at birth in the mother, infant, and in cord blood. Then, levels were followed monthly until undetectable.  Among women receiving IFX, two were receiving 10 mg/kg/dose.  Women were identified through the Crohn’s Colitis Foundation of America Pregnancy IBD and Neonatal Outcomes (PIANO) Registry.

Results:

  • IFX was detectable for 2-7 months postpartum (median interval prior to delivery and last dose was 35 days).  Median IFX level in the cord was 160% that of the mother.
  • ADA was detectable for at least 11 weeks in infant’s circulation (median interval prior to delivery and last dose was 5.5 weeks). Median ADA in the cord was 153% of the mother.
  • Median CZP in the cord was 3.9% that of the mother.
  • No congenital anomalies or complications were reported in any of the infants.

Bottomline from these studies:

Stopping these drugs after the second trimester lowers the level of these medications in the infant.  This likely results in a lower likelihood of the infant developing an opportunistic infection but also results in a low risk for the mother of an IBD flareup.  Certolizumab pegol has very low levels of placenta transfer.

Related references:

  • -J Am Acad Dermatol 2011; 65: 870.  Death noted in infant whose mother took IFX after BCG vaccination.
  • -J Crohns Colitis 2011; 5: 555-8.  Low levels of IFX detected in infants from nursing mothers with IBD  (1/200th of the maternal level in serum 2 to 3 days after infusion).
  • -Clin Gastroenterol & Hep 2010; 8: 509. n=2377. Crohn dz assoc w prematurity but not birth defects.
  • -Gastroenterol 2003;124: 9-17. Safety of 6-MP in pregnancy. n=155, at least 1 pregnancy. No adverse effect noted.
  • -Clin Gastroenterol & Hepatology; 2006: 4: 1255.  Infliximab crosses placenta but was not detected breastmilk.

Monitoring TNF antagonists in inflammatory bowel disease

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Previously, this blog has discussed the use of drug monitoring in inflammatory bowel disease (Drug levels for inflammatory bowel disease | gutsandgrowth).  A good review of this topic has been published recently (Clin Gastroenterol Hepatol 2012; 10: 1079-87).

Some of the useful pointers:

  • Factors that influence clearance of TNF antagonists are reviewed:
  1. Antidrug antibodies (ADA) increase clearance and worsen outcomes
  2. Use of concomitant immunosuppressives reduces the likelihood of ADA formation and increase drug concentration.   In the SONIC trial, use of azathioprine was associated with trough infliximab (IFX) levels of 3.5 μg/mL compared with 1.6 μg/mL with monotherapy.  Also, ADA was reduce: 0.9% compared with 14.6% in the monotherapy group. [Other studies though have found variable effects of cotherapy.]
  3. Low serum albumin and high CRP are associated with increased drug clearance
  4. Individuals with high body size and males are more likely to have increased drug clearance.
  • Better assays for measurement of IFX and adalimumab (ADL) are now available.
  • Currently a trial evaluating trough levels is underway: Trough Level Adapted Infliximab Treatment (TAXIT).  With this study, the accepted target range for trough levels is 3-7 μg/mL.  Levels >7 μg/mL are considered supratherapeutic and allows for a prolongation of dosing interval.  Preliminary data confirm that trough levels inversely correlate with CRP.
  • Proposed algorithm in individuals with loss of response & positive ADA.  If ADAs present at high titer, then switch to different TNF antagonist.  If low  titer, could either switch or attempt drug escalation.
  • With IFX, when antibodies to infliximab (ATIs) are present, the likelihood of responding to increased dose is less than 20% whereas changing to different TNF antagonist has about an 90% response (in patients who were previous responders).
  • Proposed algorithm in individuals with loss of response & negative ADA.  If subtherapeutic trough levels (IFX ❤ μg/mL, ADL <8 μg/mL, or certolizumab <27.5 μg/mL), then dose escalation is worthwhile.  If drug levels are therapeutic, then dose escalation will not be effective.
  • With IFX, more than 85% of patients will respond to drug escalation when the trough level is subtherapeutic. This is much more favorable than switching agents.
  • One other issue with ADAs is that they may be transient is some patients.  Perhaps one-fourth of ATIs may be transient which may explain why some individuals with ATIs may still respond to dose escalation.

These points give several reasons why drug monitoring is useful in individuals with loss of response and may help determine whether patients responding to therapy may be able to prolong dose intervals.  At the same time, when an individual is not responding to therapy, it is also important to determine if in fact active inflammation is present with objective markers and to consider alternative explanations for GI symptoms (eg. Clostridium difficile infection, irritable bowel, bacterial overgrowth, etc.).

Related blog entries:

Only one chance to make first impression | gutsandgrowth

When nothing else is working | gutsandgrowth

Infliximab for children with Ulcerative Colitis | gutsandgrowth

Adalimumab for children with Crohn’s disease | gutsandgrowth

CHOOSE TNF TRIAL | gutsandgrowth

CHOOSE TNF TRIAL

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While most physicians consider drug efficacy as the most important factor in choosing therapy, this is not always the determinant factor in patient choice.

The “CHOOSE TNF TRIAL” (Inflamm Bowel Dis 2012; 18: 1523-30) was a prospective survey of 100 adult patients with Crohn’s disease who were naive to anti-TNF therapy (infliximab, adalimumab, certolizumab).

Most important to patients:

  • Ease of use 69%
  • Time for therapy 34%
  • Time between applications 31%
  • Evidence for efficacy 19%
  • Fear of syringes 10%

Patient choice: Adalimumab preferred in 36%, certolizumab in 28%, and infliximab in 25%

While patient concerns need to be considered, others have shown that physician opinion is an important factor for patient decisions (J Rhemumatol 2008; 35: 618-24).  The discussion notes that “three anti-TNF drugs used in inflammatory bowel disease treatment have not been compared side-by-side in clinical trials.”  Thus far in pediatrics, infliximab is the only TNF approved for clinical use; as such, the other anti-TNF agents have been used primarily when infliximab loses effectiveness.

One drawback with injectable medications has been reduced adherence; up to 50% of patients fail to maintain regular injection interval; in addition, in patients who have had intravenous infusions (rather than patients who are naive) it is preferred over injections (Jay Popp, medical director of Janssen pharmaceuticals–personal communication).

As such, when patients receive infusions (eg. infliximab), closer followup and better adherence are more likely in comparison to injections.  This certainly improves efficacy.

Related blog entries:

TNF-α antagonists and infections

Disease modifying treatment in IBD

Only one chance to make first impression

More on IBD medicine risks

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As noted in a recent post (Assessing and discussing risk of lymphoma in IBD), diagrams can be useful to convey the absolute risks for IBD medicines; this risk is often poorly understood by patients and their families. Two articles add additional insight that may help with counseling. (Thanks to Ben Gold for forwarding these articles.)

  • Am J Gastroenterol 2012; 107: 964-70.
  • Am J Gastroenterol 2012; 107: 1051-63.

The first article reviews the risk of lymphoma with regard to inflammatory bowel disease treatment decisions.  Important points in this article include the following:

1. Relative risks may appear large while absolute risk may be quite low.  The estimate for absolute risk for lymphoma:

  • For azathioprine or 6-mercaptopurine: 1 additional case for every 4357 persons treated
  • For anti-TNF (infliximab, adalimumab, certolizumab): 1 additional case for every 2380 persons treated between ages 20-29.

2. Framing the discussion with regards to risk of continued active disease, continued exposure to steroids, and potential need for surgery can be helpful:

  • “It would take only three patients discontinuing their azathioprine to cause one additional relapse of IBD per year”
  • Seven patients stopping anti-TNF therapy would result in an additional hospitalization each year and 14 patients stopping anti-TNF therapy would result in an additional abdominal surgery each year
  • While the ‘relative risks of lymphoma associated with these medications may sound inappropriately large…A more appropriate comparison is the absolute risk of lymphoma versus the absolute risk of active/untreated disease or corticosteroid therapy.’  An example: if 2000 patients with IBD took one of these medications (eg. anti-TNF agent), probably one patient will develop a lymphoma; however, if none of those patients took an anti-TNF agent, it would result in more than 100 hospitalizations and nearly 60 surgeries.

3. “Patients can also be very sensitive to numerators and pay relatively insufficient attention to denominators.” This has been called “anchoring and adjustment” or “base-rate neglect.”  This issue has to do with “numeracy;” this is defined as the basic math skill needed for health-related activities. To help families, consider the following:

  • avoid labels such as “very low” when describing risk
  • use absolute risk data
  • use similar denominators when comparing risks
  • use visual aids

The second study cited is a pooled analysis of infections, malignancy, and mortality risks associated with infliximab and immunomodulator treatment in adult IBD patients.  This study collected safety data from 10 previous trials.  Five of these trials were randomized, controlled studies.  Table 3 and Table 4 detail extensive safety data for immunomodulators (eg. azathioprine) and for infliximab respectively.

With regard to immunomodulators, the combined studies enrolled 947 on immunomodulators in comparison to 1170 without immunomodulators.  With ulcerative colitis (UC) patients but not with Crohn’s disease (CD), immunomodulator use increased the risk of infections (120/100 patient years versus 92.5 among placebo-treated patients).  CD patients, but not UC patients, had an increased risk of malignancy with immunomodulator use (1.84/100 patient years compared with 0/100 patient years in the control group).  With the exception of the SONIC study, use of immunomodulator was not randomly assigned.  So, some of the increased risk in these patients could be due to having more severe IBD rather than due to the medication.

With regard to infliximab, and in contradiction to the previous article’s estimated risks, infliximab treatment did not appear to affect the incidence of infection, mortality, or malignancy.  This study and several others have not demonstrated an increased risk of malignancy with infliximab. This could be that even with this pooled data it is difficult to detect a rare adverse outcome.  More prospective studies and more long-term followup will be needed to truly determine the risk.

While it is known that these agents may increase the risk of some infections, the limited increase in infections which was detected only with immunomodulator use in UC is likely due to a lowered risk of infection when active inflammatory bowel disease is controlled.  A much bigger risk factor for infection is the use of corticosteroids.  When effective IBD medications are administered, this helps control inflammation and allows tapering of corticosteroids.

Related posts:

TNF-α antagonists and infections

Disease modifying treatment in IBD

Only one chance to make first impression

TNF-α antagonists and infections

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In our pediatric patients who receive tumor necrosis factor-α (TNF-α) antagonists, fortunately we see few infectious complications.  In older patients, infections are much more important source of morbidity.  The main TNF-α inhibitors in clinical use include infliximab, etanercept, adalimumab, and certolizumab. Two large studies help quantify this risk:

  • Grijalva CG et al. JAMA 2011; 306: 2331-39.
  • Strangeld A et al. Ann Rheum Dis 2011; 70: 1914-20.

The first study assembled retrospective cohorts between 1998-2007 with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis/psoriatic arthritis or ankylosing spondylitis (group 3).  This study’s acronym is SABER: Safety Assessment of Biologic Therapy. This data was compiled from 4 large US automated databases.  In total, there were 10,484 RA, 2323 IBD, and 3215 group 3 patients.  1172 serious infections were identified, mostly (53%) pneumonia or skin/soft tissue infections.  Among IBD patients, hospitalization rates were 10.91 (per 100 person-years) for TNF-α antagonists and 9.6 for comparison group.  The rates of hospitalization were similar in RA (8.16 with TNF-α antagonists) and lower in the group 3 patients (5.41 with TNF-α antagonists).   In all groups, baseline glucocorticoid use was associated with a dose-dependent increase in infections.  Overall, there was not an increase risk of hospitalizations with TNF-α antagonists compared with nonbiologic treatments.

The second cited reference examined patients from Germany with RA, enrolled in the RABBIT registry.  Data was available for 5044 patients.  There were 392 serious infections in this cohort with fewer infections noted after 3 years.  Risks for infection included age (>60), chronic lung or renal disease, history of serious infections, and treatment with glucocorticoids.  Treatment with 7.5-14mg conferred at relative risk (RR) of 2.1; treatment with ≥15mg conferred a RR of 4.7.  The rates of serious infections has an exponential change when risk factors are added together.  In Figure 3, estimated risk of serious infections for patients receiving ≥15mg  glucocorticoids along with three additional risk factors was 45% per year; with two risk factors the risk was approximately 20% and with one additional risk factor approximately 10%.

While these studies confirm significant risks of infections with biologic agents, the absolute risk is low particularly when other risk factors are not present.  In pediatric populations, glucocorticoids are the most prominent risk factor.  In addition, the risk of serious infections may be reduced by effective therapy.  In the SONIC study, serious infectious complications were less frequent in patients on combination therapy (infliximab and azathioprine) than with either monotherapy.  This result was likely due to the decreased need for glucocorticoids.

Additional references/relevant previous blogs:

  • NEJM 2010; 362: 1383. Sonic study. Combination AZA/IFX with greater efficacy. 56.8% remission in combo Rx.
  • -IBD 2008; 14: 721.  Pneumocystis jiroveci (carinii) w infliximab -review of 84 cases.  Dig Dis Sci 2007; 52: 1481-84.  PCP most likely to occur on average 3 weeks after 2nd infusion (possibly due to concommitant drug use)
  • -Gastroenterology 2008; 134: 929.  n=100 consecutive IBD patients with opportunistic infections.  Any of drugs associated w ~2.9 OR in adutls (greatest in >50yrs).  OR 14.5 when multiple immune drugs. Steroids more associated with Candida. AZA/6MP more with viral: HSV, VZV (shingles), CMV.  IFX less commonly with infections -though increased histoplasma and atypical mycobacterium
  • -Gastroenterology 2009; 136: 1182.  Review of biologics.
  • -IBD 2007; 13: 769.  Review of safety of wide range of biologics
  • –Clin Gastroenterol Hepatol. 2006; 5:621-30.  TREAT registry.  Steroids but not biologics associated with increased mortality risk.
  • Only one chance to make first impression

Infliximab for children with Ulcerative Colitis

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A large multicenter study of patients 6-17 years of age has shown that infliximab (IFX) can be effective for ulcerative colitis (UC) (Clin Gastroenterol Hepatol 2012; 10: 391-99). Our pediatric GI group was part of this multicenter study which enrolled 60 patients. Stanley Cohen was lead CCDHC investigator and is one of the authors.

At week 8, 44 patients (73.3%) had a clinical response to IFX.  This group of ‘responders’ were eligible for the maintenance phase of the study and were divided into a q8 week treatment group (Q8) and a q12 week treatment group (Q12).  During the maintenance phase, patients who had lost response were eligible to have a dose escalation from 5 mg/kg/dose to 10 mg/kg/dose. At week 54,  patients receiving every Q8 had a remission rate of 38% (8 of 21) whereas among the Q12 responder group only 18% (4 of 22) were in remission.  Overall, the authors projected that if the entire cohort had been placed on every 8 week treatment, the response would have been 28% at week 54; in addition, analysis with ‘real-world’ dose adjustments could achieve a 42.8% remission rate.

The main serious adverse events reported during the study was worsening of UC.  Two patients were receiving immunomodulators during the study. Five of 60 patients required a colectomy within the 54-week study period.

The risk/benefit ratio of TNF antagonists for UC has been discussed in related posts (see below).

Previous related posts:

TNF antagonists and UC

Only one chance to make first impression

Additional references:

  • -Am J Gastroenterol (Oussalah A et al) 2010; 105: 2617-25. Multicenter study of IFX for UC.
  • -Gastroenterology 2010; 138: 2282. Severe pediatric UC. 25/33 responded to IFX. colectomy rate 19% at 1 year.