This non-interventional, multicenter, prospective cohort study was managed in cooperation with an independent scientific committee including one methodologist and one office-based and three hospital-based rheumatologists.
Included patients were followed over an 18-month period, with data collected at follow-up visits around months 3, 6, 9, 12, and 18 when performed.
According to French legislation regarding non-interventional studies, the TANDEM protocol (NCT02608112) was approved by the “Comité Consultatif sur le Traitement de l’Information en Matière de Recherche dans le Domaine de la Santé” (Consultative Committee on Information Processing for Research in the Field of Health) and by the Ethic Committee “Commission Nationale de l’Informatique et des Libertés” (Independent Administrative Authority Protecting Privacy and Personal Data) (authorization DR-2015-415), which guarantees confidentiality to the subjects. All patients were informed about the study before enrollment and had no objection to sharing their data. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments.
From the 1675 hospital- and office-based rheumatologists regularly managing patients with RA who were invited to participate in the study, 189 physicians (11%) agreed, and 107 (6%) investigators included at least one eligible patient in the TANDEM study from December 2015 to December 2016. The last patient last visit was performed on July 2018. Amongst the 94 main sites (88%) that participated in this real-world study, 10 (11%) delegated patient follow-up to at least one satellite site, i.e., after the first TCZ-SC prescription from hospital (done in France for all patients with RA), patients could be followed by an office-based rheumatologist if they usually did so.
Patients eligible for the study were adults for whom the specialist decided to initiate treatment with TCZ-SC (either in combination with a csDMARD or in monotherapy) for moderate to severe RA prior to inclusion and who agreed to participate. Previous treatment with TCZ and participation in a clinical trial on RA were exclusion criteria.
At inclusion, upon initiation of TCZ-SC treatment, the following data were collected: patient’s characteristics, medical history, RA history and previous treatments, disease activity [Disease Activity Score 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), patient’s and physician’s visual analogue scale (VAS) on global assessment of disease activity], and use of TCZ-SC.
During the follow-up visits (around months 3, 6, 9, 12, and 18), use of TCZ-SC and other RA treatments, RA activity, and adverse events (AEs), including AEs of special interest (AESIs: anaphylaxis/hypersensitivity reactions, demyelinating disorders, gastrointestinal perforations, malignancies, myocardial infarctions, strokes, and serious and/or medically significant infections, hepatic events, and bleeding events) were collected.
During the study, patients completed self-reported questionnaires to describe their disability, quality of life, and TCZ-SC compliance, using respectively the Health Assessment Questionnaire Disability Index (HAQ-DI) at inclusion, around months 6 and 12, the EuroQol Group-5 Dimensions 3 Levels (EQ-5D-3L, dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) at inclusion, around months 3, 6, and 12, and the 5-item Compliance Questionnaire for Rheumatology (CQR5) at inclusion, around months 3, 6, 12, and 18.
Study Size and Statistical Methods
The primary criterion of this descriptive study was defined as the proportion of patients still receiving TCZ-SC 12 months after the first injection. Based on literature data on TCZ-IV, a drug retention rate of 65% was expected for TCZ-SC at month 12 . Under this assumption, 286 patients with RA had to be included to meet the study’s primary objective with an absolute precision of ± 6.0% and a 95% confidence interval (CI), and assuming 15% of unevaluable patients for the primary criterion.
Statistical analyses were performed using SAS® software (version 9.4). All tests were two-sided with an α risk at 5%.
Efficacy analyses were carried out on the population of included patients having signed an informed consent and with at least one documented TCZ-SC injection (efficacy population). Safety data were analyzed on the population of patients having signed an informed consent and with at least one TCZ-SC injection (safety population).
The drug retention rate was estimated in the overall efficacy population at each follow-up time point, using the Kaplan–Meier method. The associated 95% CI was provided using the Greenwood formula. The drug retention rate was also estimated in patient subgroups defined at inclusion (i.e., at the time of the first TCZ-SC injection): modality of use of TCZ-SC (monotherapy, MONO; with combined csDMARDs, COMBO), patient age (≤ 65 years, > 65 years), body mass index (BMI; ≤ 30 kg/m2, > 30 kg/m2), weekly MTX dose (no MTX, less than 10 mg, between 10 and 15 mg, between 15 and 20 mg, and more than 20 mg). Between-group comparisons were performed using log-rank tests.
All the TCZ-SC effectiveness parameters were described at each study time point. The proportions of patients in DAS28-ESR remission and low disease activity (LDA) (< 2.6 and ≤ 3.2, respectively), SDAI remission and LDA (≤ 3.3 and ≤ 11), and CDAI remission and LDA (≤ 2.8 and ≤ 10) were notably described during follow-up (analyses performed on observed data). Patient-reported outcomes (HAQ-DI, EQ-5D-3L, and CQR5) were described at each study time point according to authors’ recommendations. Considering CQR5, high adherers to TCZ-SC were defined by an injection rate of at least 80% of the theoretical injections.
Safety data were described in the overall safety population and according to the use of TCZ-SC (MONO and COMBO) and the patient’s age at first injection (± 65 years). For serious AEs (SAEs), the incidence rates were also provided per 100 patient-years (PY).