2. Methods
2.1 Search strategy
A systematic review was conducted according to the Preferred Reporting
Items for Systematic Reviews and Meta-analysis (PRISMA) Statement
(supplementary figure S1) [29]. The protocol for this study was
registered on the website of PROSPERO International Prospective Register
of Systematic Reviews (https://www.crd.york.ac.uk/prospero/),
registration number CRD42020197101. Embase, Medline, Cochrane Central,
and Web of Science were searched from 1946 to June 29, 2020. The search
was conducted utilizing the PICOS format (Patients, Interventions,
Comparators, Outcomes and Studies) as follows: P: adult participants
(age > 18 years) with IBD; I: received VDZ
treatment; C: control group given placebo; O: arthralgias; S: RCTs.
Manual searches of reference citations in the reviewed literature
sources was subsequently performed. A detailed description of the search
strategy is provided in supplementary figure S2. Two authors (from
among: JBS, MT, EI, HK) independently reviewed each of the titles and
abstracts for eligible studies. All disagreements were resolved by
consensus among the authors.
2.2 Eligibility criteria
Eligibility was limited to: (1) studies involving humans; (2) with> 18 year-old participants enrolled; (3) which were
RCTs comparing treatment with VDZ versus placebo; (4) with atleast one
case of new-onset arthralgia reported within the listed AEs. Studies
were excluded if: (1) they were abstracts, case-reports, editorials,
comments, letters, reviews, meta-analyses, observational studies, or
open-label trials; (2) duplicate; or (3) written in languages other than
English or without English translated versions available.
2.3 Study selection
Two researchers (from among: JBS, MT, EI, HK) independently performed
the initial screening of each paper by title and abstract. Full texts
were retrieved for all articles which were deemed potentially eligible,
and were screened accordingly. Any disagreements were resolved by
consensus among the researchers.
2.4 Data extraction and synthesis
The selected studies were reviewed with the data extracted independently
by two researchers (JBS, MT). Conflicting data was resolved by consensus
between the researchers. Information related to author, publication
year, country/region, study type, sample size, age, and outcomes were
put into a bibliographic database using Microsoft® Office Excel® version
14.0 software (Microsoft, Redmond, WA, USA). Corresponding authors were
contacted by email to provide additional data where needed. Among papers
describing the same cohort of patients, the most up-to-date study was
considered for inclusion.
2.5 Assessment of risk bias and quality
The risk of bias of the RCTs was evaluated using the Cochrane
Collaboration’s tool, evaluating sequence generation, allocation
concealment, blinding, incomplete outcome data, selective outcome
reporting, and other sources of bias [30]. The included studies were
stratified according to risk of bias. The GRADE (Grading of
Recommendations, Assessment, Development and Evaluations) approach was
used to rate overall quality of the evidence [31]. Two reviewers
(from among: JBS, YGP, MT) independently assessed the risk of bias and
evaluated the quality of each of the included papers. Disagreements were
resolved by consensus among the researchers.
2.6 Data collection
A narrative synthesis of the included studies was performed around the
sample size, disease population, participant demographics, baseline
disease activity, length of disease, prior immunosuppressive treatments,
presence of arthralgias, other side effects to treatment, odds ratio
(OR), and 95% confidence interval (CI) measurements.
2.7 Ethical considerations
Due to the nature of this study, a systematic literature review, there
was no need for institutional review board approval.