Download Use of Tumor Necrosis Factor Alpha Blocking Agents in the

Running hear: TUMOR NECROSIS FACTOR BLOCKING AGENTS
Critically Appraised Topic
Use of Tumor Necrosis Factor α Blocking Agents in Ulcerative Colitis Patients
Dwight Remington
University of Mary
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Use of Tumor Necrosis Factor α Blocking Agents in Ulcerative Colitis Patients
Author: Dwight Remington
Date: June 11, 2016
Clinical Scenario:
A 32-year old male patient presented to the clinic with complaints of abdominal pain, weight
loss, diarrhea 10-15 times a day, and blood in stool a few months ago. The patient has had a
colonoscopy completed and the diagnosis of ulcerative colitis that is limited to the rectum was
determined. The patient has been tried on oral corticosteroids, sulfasalazine, mesalamine, and
balsalazide without much improvement. The patient is in the clinic today inquiring about the
use of biologic agents seen on television advertisements for ulcerative colitis.
PICO Question:
Do patients with ulcerative colitis experience a decrease in symptoms and outbreaks when using
tumor necrosis factor α blocking agents, when compared to those that do not?
Summary and Appraisal of Key Evidence:
Yun-Na, S., & Ping, Z. (2015). Efficacy and safety of tumor necrosis factor-α blockers for
ulcerative colitis: A systematic review and meta-analysis of published randomized
controlled trials. Journal Of Food & Drug Analysis, 23(1), 1-10.
Yun-Na and Ping (2015) authored a meta-analysis of multiple randomized controlled
trials making it a level I source of evidence. The meta-analysis was constructed to evaluate both
the safety of using tumor necrosis factor α blocking medications, as well as the efficacy of these
medications in the treatment of ulcerative colitis. There were nine studies that analyzed the
treatment of 2,518 patients included in the meta-analysis. All of the studies were randomized
controlled trials that either compared the tumor necrosis factor α blockers to a placebo or to
corticosteroids. The success of treatment was determined by short term clinical response and
remission, long term remission, healing of the mucosal lining, the presence of adverse effects
and the need for a colectomy.
Short term response and remission was measured as 2-8 weeks while long term response
was measured over 12 weeks to 10.9 months. The use of tumor necrosis factor α blocking agents
showed a statistically significant improvement over the use of a placebo for reducing patient
symptoms. When the same medications were evaluated for the ability to produce long term
remission the tumor necrosis factor α blocking agents performed better than the control groups in
all studies. The ability of therapy to induce mucosal healing has become a measurement for
efficacy of treatment for ulcerative colitis. The healing of the mucosal tissue is important for the
patient to have a decrease in symptoms and could play a role in decreasing the frequency of
relapses. The use of tumor necrosis factor α blocking agents showed the ability to increase
mucosal healing.
The safety of the medications must be analyzed before patient use. The safety of the
agents was measured by the number of serious adverse reactions that were reported in six of the
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randomized controlled trials. There were adverse reactions reported, but not at a higher rate than
in any other population. Four of the trials investigated the tumor necrosis α blocking agents’
effects on colectomy rates from the disease process. The trials showed that the need for a
colectomy in the short term was reduced, but may not be changed over the long term course of
the disease.
Stidham, R. W., Lee, T. H., Higgins, P. R., Deshpande, A. R., Sussman, D. A., Singal, A. G., &
... Waljee, A. K. (2014). Systematic review with network meta-analysis: the efficacy of
anti-tumor necrosis factor-alpha agents for the treatment of ulcerative colitis. Alimentary
Pharmacology & Therapeutics, 39(7), 660-671.
Stidham et al. (2014) authored a systematic review of seven randomized controlled trials
focused on the efficacy of treatment for ulcerative colitis using tumor necrosis factor α blocking
agents. Because the information was created by a systematic review, the findings are level I
evidence. The tumor necrosis factor α agents used in the studies were infliximab, adalimumab,
and golimumab. The randomized controlled trials analyzed compared the agents in question to a
placebo. There was also a cross agent comparison completed between the medications to
establish any differences in efficacy.
The patient responses to therapy varied based on what was being evaluated. The ability
of the agents to induce a remission was evaluated using an ulcerative colitis symptom score and
was evaluated within 8 weeks of starting therapy. The ability of the medications to maintain
efficacy and response was measured after 52 weeks of therapy. The ability of the medication to
maintain a remission once induced was measured after 52 weeks of therapy.
The meta-analysis of the five selected studies showed that the tumor necrosis factor α
blocking agents were efficacious in eliciting a remission and also maintaining the remission
state. The tumor necrosis factor α blocking agents showed a 2-fold increase in the likelihood of
a patient to maintain a remission and a 1.76-fold increase in the likelihood of continuing to have
a therapeutic response when compared to patients receiving a placebo. There was also a cross
agent comparison completed to try and determine if any of the tumor necrosis factor α blocking
agents were more effective than the others. Comparing the efficacy of the agents showed no
statistically significant differences between the agents in the ability to either induce or maintain a
remission.
Clinical Bottom Line:
Tumor necrosis factor α blocking agents have been proven to be more effective in both induction
and maintenance of remission from ulcerative colitis. The agents have also been shown to
increase mucosal healing of damaged tissue from ulcerative colitis while showing no significant
increase in serious adverse reactions.
Implications for Clinical Practice
Tumor necrosis factor α blocking agents are not first line agents for mild ulcerative colitis, but
provide a safe and effective option for patients suffering from moderate or severe disease that
has proven refractory to conventional therapies and treatment strategies. The efficacy does not
appear to differ between the available tumor necrosis factor α blocking agents.
TUMOR NECROSIS FACTOR BLOCKING AGENTS
References
Stidham, R. W., Lee, T. H., Higgins, P. R., Deshpande, A. R., Sussman, D. A., Singal, A. G., &
... Waljee, A. K. (2014). Systematic review with network meta-analysis: the efficacy of
anti-tumor necrosis factor-alpha agents for the treatment of ulcerative colitis. Alimentary
Pharmacology & Therapeutics, 39(7), 660-671.
Yun-Na, S., & Ping, Z. (2015). Efficacy and safety of tumor necrosis factor-α blockers for
ulcerative colitis: A systematic review and meta-analysis of published randomized
controlled trials. Journal Of Food & Drug Analysis, 23(1), 1-10.
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