Article Analysis: The Efficacy and Safety of Rituximab in Patients With Active Rheumatoid Arthritis Despite Methotrexate Treatment

This article analysis examines the efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment. The study focuses on a randomized controlled trial and evaluates the allocation of participants, blinding of participants and study personnel, and the presentation of results. The main result of the study shows that rituximab is effective and well tolerated in MTX therapy for patients with resistant rheumatoid arthritis.

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Article Analysis:
Emery, P. et al., 2006. The Efficacy and Safety of Rituximab in Patients With Active
Rheumatoid Arthritis Despite Methotrexate Treatment. Arthritis & Rheumatism, 54(5), p. 390–
1400.
Student’s Name
University
Date
University

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Article Analysis:
Emery, P. et al., 2006. The Efficacy and Safety of Rituximab in Patients With Active
Rheumatoid Arthritis Despite Methotrexate Treatment. Arthritis & Rheumatism, 54(5), p.
390–1400.
1. Did the study ask a clearly focused question?
Emery, et al. (2006, p. 390–1400) study question is clear and has been stated on the objective.
The reader can easily understand the nature of the study as a randomized control trial because
from the objective and the question we can identify the study population as being patients with
rheumatoid arthritis that is resistant to antirheumatic drugs. Thus the results to be expected are
the efficacy and safety of the patient when they use rituximab in this condition. A randomized
control trial is supposed to have the control group and the general group where measures are
determined. This means that the reader can easily understand the focus of the study and the main
outcomes that will be measured in the study. As such, it becomes easy to determine what the
study is seeking to present.
2. Was this a randomized controlled trial (RCT) and was it appropriately so?
This study was carried out to determine the best way of dealing with rheumatoid arthritis that is
resistant to antirheumatic drugs. Thus the focus of the study was to determine if rituximab can be
effective in treating this type of condition. Through the use of controlled groups, it becomes easy
to determine how the drug is effective by comparing the results from the two groups.
Randomized controlled trials have been described as the best studies for determining the effects
between different groups through having a control group and the general group. The focus is to
determine how effective the study can be done. By using the blinded study approach, the
effectiveness of the study is increased since the participants are not aware of the study processes

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and do not understand the difference between the control group and the main group. Further, the
control trial was appropriate because patients were analyzed in their settings making it easy to
measure the maximum effects of the control that the patient deals with (Broekhuizen, et al. 2015,
p. 5). This research approach was fit for the study problem because it becomes easy to measure
the differences between groups when controls are used rather than studying all patients in the
same way. The difference between the control group and the main group is what defines the
control trial and gives the method effective ways of gathering and presenting research findings
since the results are based on comparing the two groups. By using the IIb, randomized, double-
blind, double-dummy, placebo-controlled, offers the best results since the placebo effect is used
to measure the effects of the treatment by not depending on the treatment itself. This increases
the findings since the researchers use the placebo to compare the results of the other real control
group. Unlike the common control trial where results are compared between the treatment and
the control group, this study allows the researcher to produce better results by comparing the
placebo with the control group.
3. Were participants appropriately allocated to intervention and control groups?
The inclusion criteria for the patients were aged between 18-80 years, had been diagnosed with
the condition, and have been on ongoing treatment of MTX for at least 12 weeks before the study
began. This means that they must have failed in the previous treatment showing no signs of
response. The patients were randomly placed in the two groups during admission to the facility
without knowing which groups they belonged to. Blinding was used so that patients do not have
preferences on either of the two groups based on the fact that the study was testing a new
treatment option for the condition. The primary analysis for the study was the intent to treat with
non-responders imputed for all categorical endpoints. The logistic regression model was used to

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evaluate the ACR20 response at week 24 in all the study groups. The effectiveness of the study
was based on the fact that the participants were measured in their groups to increase the validity
of the results of the study. The groups were balanced since the allocation was uniform ensuring
that those who were put in each group were the same as those in the other group. The
participants were stratified by region to make it easy to follow up and gathering of information.
By grouping them in regional strata, demographic factors that relate to how the patients respond
to medication are captured in the study thus increasing the validity of the findings.
4. Were participants, staff and study personnel ‘blind’ to participants’ study group?
This study was a double-blind one, which means that both the patients and the researchers
were blinded and did not know the difference between the two groups. By blinding a study, bias
is reduced from patients since they may have higher expectations and at the same time may
report biased results when they understand that there are two different groups of the study. The
placebo method was used to reduce bias between the patients by ensuring that all patients
received
On the other hand, the researchers were blinded so that the effectiveness of the placebo can be
increased (Probst, et al., 2016., p. 4). In this case, the focus is on recording the actual findings
that the patients report without knowing the measure that was used so that the effectiveness of
the research can be increased. In this study, Glucocorticoids were used to make the patients feel
like the treatment was being administered to them but the control group was given rituximab
through intravenous injection. This makes it difficult for the patients to understand the
differences between the two groups thus increasing the validity of the findings.

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For researchers, the blinding was used to reduce their reporting bias and use of assumptions on
reporting the findings. The fact that they did not know the difference between the two groups
means that the validity of the findings is increased since the researchers have to only report the
findings that they gathered from the study.
5. Were all of the participants who entered the trial accounted for at its conclusion?
Yes, all the participants were accounted for including those who dropped off during the study.
Like any other study, there was a loss in follow up where some of the participants dropped off
during the two weeks follow up but the researchers only accounted for those who participated in
the end. The participants were analyzed with the intention to treat based on the groups that they
belonged to. By analyzing patients within the groups that they belonged to, the findings of the
study were analyzed based on the intention to treat through understanding the relationship
between the two groups.
To increase the validity of the findings, all participants were the same at the beginning of the
study and entering the placebo stage. However, I think the period of follow up of two weeks was
too long since some of the effects of the failure of the drug may be immediate while there are
other factors that reduce or increase the severity of the pain. This means that it would have been
better if all the patients in the study were admitted inwards so that they can be monitored in
clinical settings. In this case, there are other social determinants of health that may affect the way
people respond to medications within clinical settings.
6. Were the participants in all groups followed up and data collected in the same way?
The participants were followed up for 24 weeks of study to measure the response to the drug and
the effects that they displayed in the control group. The same intervals of treatment and

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assessment were used to reduce performance bias and increase the effectiveness of the drugs.
Stratifying the participants in regions ensured that they are assessed within the clinical conditions
of the region that they come from to reduce performance bias. When participants are assessed at
the same time by considering different factors that affect them, bias is reduced and validity
increased (Hrobjartsson, et al., 2014, p. 1278)
7. Did the study have enough participants to minimize the play of chance?
This study did not have the power of calculation nor were the participants sampled to determine
the number of respondents that were to be included in the study. In randomized control trials, the
sample size is based on the primary outcome of the study. In this case, the nature of the study
was clinical superiority design which means that the power calculation could have been used to
determine the number of people who could have participated in the study. The role of using the
power of calculation is to ensure that the study uses an appropriate sample size for the research
that can allow generalization of the findings (Zhong 2019, p. 52). If the sample frame is too
small, it becomes difficult to generalize the findings of the study since they feel to represent the
whole population that the study relates to.
8. How the results presented and what are is the main result?
The results have been statistically presented by focusing on the themes in the study and use of
graphs and tables to present the different responses that the patients displayed during the study.
This is to increase the easy understanding of the study findings and increasing their validity.
The main results of the study showed that patients who received rituximab showed 20%
improvement at week 24 which was seen in 55% of the population as compared to 28% in the
general group. ACR50 responses were achieved at 33%, 34% and 13% of the patients and at the

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same time ACR70 responses were achieved by 13%, 20%, and 5% of patients. The study also
reported that Glucocorticoids have no effects on reducing pain in the patients at the end of week
24. Thus this study concluded that rituximab dose is effective and well tolerated when used in
MTX therapy for the patients in this study.
9. Can the results be applied in your context? (or to the local population?)
Colquitt & George (2011, p. 433) suggests that a good study is supposed to add knowledge to the
field of practice and at the same time form directions for future research. The study builds on the
effects of rituximab in the treatment of rheumatoid arthritis that is resistant to antirheumatic
drugs. By using a control group and following up the participants for a 24 week period, the study
reported that the drug is effective in treatment. Twisk et al. (2018, p. 84) suggest that randomized
control trials can only be valid if their findings can be applied to the general field. This means
that the findings of the study acknowledge the use of rituximab in the treatment of the patients
with the disease since it yields better results even in resistant conditions. Thus the findings of the
study are applicable to the discipline since they form the basis on which research needs to be
done to determine the best way that rituximab can be used in clinical settings for patients with
resistant rheumatoid arthritis. According to Radhakrishna & Doamekpor (2008, p. 3), the
reliability of the study determines the applicability of its findings. Thus in this study, the findings
are applicable since the study was reliable, lacked bias and reported the best outcomes based on
the fact that the researchers and the participants were all blinded.
10. Were all important outcomes considered so the results can be applied?
Yes, all the important outcomes of the study were considered from the use of two groups one that
was placebo and the other one that was the treatment group. This allows the researcher to

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compare the effects of the drug in the treatment group with the placebo one. This makes the
findings reliable since the researcher follows the changes that take place within the two groups.
11. Are the benefits worth the harms and cost?
This study has more benefits than harm since it reported positive outcomes in the control group
as compared to the general group. The fact that the control patients did not report any side effects
on the use rituximab means that the study is worth and the findings can be used in other clinical
settings. Bondemark & Ruf (2015, p. 458) suggest that randomized control trials are used to
determine the effectiveness of a treatment by observing the effects in the control group. This
study did not report any side effects in the control group patients thus indicating that the drug is
effective in the treatment of resistant rheumatoid arthritis.

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References
Bondemark, L. & Ruf, S., 2015. Randomized controlled trial: the gold standard or an
unobtainable fallacy?. European Journal of Orthodontics, 37(5), pp. 457-461.
Broekhuizen, K., Pothof, A., Craen, A. J. M. d. & Mooijaart, S. P., 2015. Characteristics of
Randomized Controlled Trials Designed for Elderly: A Systematic Review. Plos One, 10(5).
Colquitt, J. & George, G., 2011. Publishing in AMJ—Part 1: Topic Choice. Academy of
Management Journal, 54(3), pp. 432-435.
Emery, P., Fleischmann, R., Filipowicz-Sosnowska, A., Schechtman, J., Szczepanski, L.,
Kavanaugh, A., Shaw, T. M., 2006. The Efficacy and Safety of Rituximab in Patients With
Active Rheumatoid Arthritis Despite Methotrexate Treatment. ARTHRITIS & RHEUMATISM,
54(5), p. 390–1400.
Hrobjartsson, A., Emanuelsson, F., Thomsen, A. S., Hilden, J., & Brorson, S., 2014. Bias due to
lack of patient blinding in clinical trials. A systematic review of trials randomizing patients to
blind and nonblind sub-studies. International Journal of Epidemiology, 43(4), pp. 1272-1283.
Probst, P., Grummich, K., Heger, P., Zaschke, S., Knebel, P., Ulrich, A., Diener, M. K., 2016.
Blinding in randomized controlled trials in general and abdominal surgery: protocol for a
systematic review and empirical study. Systematic Reviews, 5(48).
Radhakrishna, R. & Doamekpor, P., 2008. Strategies for generalizing findings in survey
research. 46(2).
Twisk, J., Bosman, L., Hoeskstra, T., Rijnhart, J., Welten, M., & Heymans, M., 2018. Different
ways to estimate treatment effects in randomised controlled trials. Contemporary Clinical Trials
Communications, Volume 10, pp. 80-85.
Zhong, B., 2019. How to Calculate Sample Size in Randomized Controlled Trial?. Journal of
Thoracic Disease, 1(1), pp. 51-54.