IDentification of Factors Predictive of Tofacitinib's Survival in Patient With Rheumatoid Arthritis
- Registration Number
- NCT03981900
- Lead Sponsor
- Pfizer
- Brief Summary
Regarding Tofacitinib, newly introduced on the market, few data on drug retention and no data on the factors predictive of Tofacitinib drug survival in patients with RA are available.
Therefore, the primary objective of the DeFacTo study will be to identify the factors predictive of Tofacitinib drug survival in patients with RA.
As secondary objectives, the impact of behavioural strategies on drug survival and other clinical parameters as well as Tofacitinib effectiveness and tolerability will be studied under real-life conditions of use in French patients with RA.
- Detailed Description
This is an observational, open-label, prospective, multi-centre, national study designed to evaluate the factors predictive of Tofacitinib's survival in patients with rheumatoid arthritis
If catastrophisation is described as a distortion of the perception of pain involving a both emotional and cognitive component, pushing the patient to see only the worst, coping involves adaptive strategies by which the patient attempts to find solutions in order to better cope with his/her disease. It has been demonstrated that such behavioural strategies can influence directly or indirectly the intensity of symptoms in patients suffering from chronic disease.
Therefore, as secondary objectives, the impact of behavioural strategies on drug survival and other clinical parameters as well as Tofacitinib effectiveness and tolerability will be studied under real-life conditions of use in French patients with RA.
The duration of this study will be approximately 48 months including a 24-month recruitment period and a 24-month patient follow-up period.
Patients will be followed prospectively and follow-up visits will be conducted after the initial consultations. No visit or additional test is required by the protocol, since the study is observational
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 314
- Patient 18 years of age or older
- Patient in whom the diagnosis of moderate to severe active rheumatoid arthritis has been confirmed by a rheumatologist
- Patient for whom the rheumatologist decides to initiate treatment with Tofacitinib
- Patient informed of the study
- Patient participating in a randomised clinical trial.
- Patient presenting with a contraindication to prescription of Tofacitinib
- Patients who are investigational site staff members or patients who are Pfizer employees directly involved in the conduct of the trial.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Rheumatoid arthritis Tofacitinib All participants with a diagnosis of moderate to severe active rheumatoid arthritis and treated with Tofacitinib
- Primary Outcome Measures
Name Time Method Duration of Tofacitinib Drug Survival Date of initiation of study drug treatment up to date of permanent drug discontinuation or date of censoring (up to a maximum of 48 months) The duration of tofacitinib drug survival was calculated as: date of permanent drug discontinuation minus date of first taking the drug + 1. If a participant did not present with the event of interest, that is they did not have a permanent drug discontinuation record during the study, then they were censored at the time of their last visit. Kaplan-Meier method was used for estimation.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Total Pain Catastrophising Scale (PCS) Score at Month 1, 3, 6, 12, 18 and 24 Baseline, Month 1, 3, 6, 12, 18 and 24 PCS is a 13 item questionnaire around thoughts and emotions experienced during pain, with each question scored on a 5-point scale ranging from 0 (not at all) to 4 (all the time), where higher scores indicated worse condition. There are three subscales of PCS: rumination (thinking deeply) \[4 items\], exaggeration \[3 items\] and helplessness \[6 items\]. Total scores and domain scores are derived by summing the scores of the individual items. Overall possible Total PCS score range is 0 to 52, where higher scores signifies worse condition. A total score of greater than or equal to (\>=) 20 indicates a clinically relevant level of catastrophising. Mean change from baseline in total PCS score is reported in this outcome measure.
Change From Baseline in Coping Strategies Questionnaire (CSQ) Score at Month 1, 3, 6, 12, 18 and 24 Baseline, Month 1, 3, 6 12, 18 and 24 CSQ evaluates cognitive coping, has 21 items and 5 domains in its French version. For each item, participants rate the frequency of their use of each coping strategy on a 4- point Likert-type scale (0= Never, 1= sometimes, 2= often and 3= very often). Domain scores are derived by summing the individual items scores that make-up the domain. Five domains with score range: distraction (5 items, score range: 0 to 15), catastrophising (4 items, score range: 0 to 12), distancing from pain (4 items, score range: 0 to 12), ignoring pain sensations (5 items, score range: 0 to 15) and praying (3 items, score range: 0 to 9). For each domain, higher scores indicated worse condition. Mean change from baseline in CSQ domain scores are reported in this outcome measure.
Percentage of Participants With Low Disease Activity (LDA) According to Disease Activity Index 28 (DAS28)-4 Erythrocyte Sedimentation Rate (ESR) (<=3.2) Baseline, Month 1, 3, 6, 12 18, and 24 DAS28-4 ESR is a composite endpoint, calculated using 4 variables (represented by '4' in the name). Components includes: Tender Joint Count (TJC) with 28 joints assessed, Swollen Joint Count (SJC) with 28 joints assessed, ESR (millimeter per hours \[mm/h\]) and Patient Global Assessment (PtGA) recorded on 100 mm VAS (scores ranging 0 \[no disease activity\] to 100 mm \[maximum disease activity\], higher scores=more disease activity). The calculation of DAS28-4 ESR is as follows: 0.56 \* square root (sqrt) (TJC) + 0.28 \* sqrt (SJC) + 0.70\* In (ESR) + 0.014\* (PtGA); where ln = natural logarithm. Total DAS28-4 score range: 0 to 9.4, higher score=more disease activity. DAS28(ESR) score of \<=3.2 indicates LDA. Percentage of participants with DAS28-4 ESR \<=3.2 is presented in this outcome measure.
Percentage of Participants With LDA According to DAS28-4 C Reactive Protein (CRP) (<=3.2) Baseline, Month 1, 3, 6, 12 18, and 24 DAS28-4 CRP is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). Components includes: TJC with 28 joints assessed, SJC with 28 joints assessed, CRP (mg/L) and PtGA recorded on 100 mm VAS (scores ranging 0 \[no disease activity\] to 100 mm \[maximum disease activity\], higher scores=more disease activity). The calculation of DAS28-4 CRP is as follows: 0.56 \* sqrt (TJC) + 0.28 \* sqrt (SJC) + 0.36 \* ln (CRP+l) + 0.014\*PtGA + 0.96; where ln = natural logarithm. Total DAS28-4 score range: 0 to 9.4, higher score=more disease activity. DAS28(CRP) score of \<=3.2 indicates LDA. Percentage of participants with DAS28-4 CRP \<=3.2 is presented in this outcome measure.
Percentage of Participants With LDA According to Simplified Disease Activity Index (SDAI) <=11 Baseline, Month 1, 3, 6, 12 18, and 24 SDAI is a composite end point, calculated as TJC + SJC (both using 28 joints) + PtGA (0-10 cm scale, higher score=more disease activity) + Physician Global Assessment (PhGA) (0-10 cm scale, higher score=more disease activity) + CRP (milligrams per deciliter \[mg/dL\]). The SDAI score is classified into four categories: remission (\<=3.3), low (\>3.3-11), moderate (\>11-26), and high (\>26) disease activity. The SDAI score ranges from 0 to 86 where higher scores indicates high disease activity. SDAI score of \<=11 indicates LDA. Percentage of participants with SDAI \<=11 is presented in this outcome measure.
Percentage of Participants With LDA According to Clinical Disease Activity Index (CDAI) <=10 Baseline, Month 1, 3, 6, 12 18, and 24 CDAI is a composite end point, calculated as TJC + SJC (both using 28 joints) + PtGA (0-10 cm scale, higher score=more disease activity) + PhGA (0-10 cm scale, higher score=more disease activity). The CDAI score is classified into four categories: remission (\<=2.8), low (\>2.8-10), moderate (\>10-22), and high (\>22) disease activity. The CDAI score ranges from 0 to 76, where higher scores indicates high disease activity. CDAI score of \<=10 indicates LDA. Percentage of participants with CDAI \<=10 is presented in this outcome measure.
Percentage of Participants With Remission According to DAS28-4 ESR<2.6 Baseline, Month 1, 3, 6, 12 18, and 24 DAS28-4 ESR is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). Components includes: TJC with 28 joints assessed, SJC with 28 joints assessed, ESR (mm/h) and PtGA recorded on 100 mm VAS (scores ranging 0 \[no disease activity\] to 100 mm \[maximum disease activity\], higher scores=more disease activity). The calculation of DAS28-4 ESR is as follows: 0.56 \* sqrt (TJC) + 0.28 \* sqrt (SJC) + 0.70\* In(ESR) + 0.014\* (PtGA); where ln = natural logarithm. Total DAS28-4 score range: 0 to 9.4, higher score=more disease activity. DAS28(ESR) score of \<2.6 indicates LDA. Percentage of participants with DAS28-4 ESR \<2.6 is presented in this outcome measure.
Percentage of Participants With Remission According to DAS28-4 CRP <2.6 Baseline, Month 1, 3, 6, 12 18, and 24 DAS28-4 CRP is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). Components includes: TJC with 28 joints assessed, SJC with 28 joints assessed, CRP (mg/L) and PtGA recorded on 100 mm VAS (scores ranging 0 \[no disease activity\] to 100 mm \[maximum disease activity\], higher scores=more disease activity). The calculation of DAS28-4 CRP is as follows: 0.56 \* sqrt (TJC) + 0.28 \* sqrt (SJC) + 0.36 \* ln (CRP+l) + 0.014\*PtGA + 0.96; where ln = natural logarithm. Total DAS28-4 score range: 0 to 9.4, higher score=more disease activity. DAS28(CRP) score of \<2.6 indicates LDA. Percentage of participants with DAS28-4 CRP \<2.6 is presented in this outcome measure.
Percentage of Participants in Remission According to SDAI <=3.3 Baseline, Month 1, 3, 6, 12 18, and 24 SDAI is a composite end point, calculated as TJC + SJC (both using 28 joints) + PtGA (0-10 cm scale, higher score=more disease activity) + PhGA (0-10 cm scale, higher score=more disease activity) + CRP (mg/dL). The SDAI score is classified into four categories: remission (\<=3.3), low (\>3.3-11), moderate (\>11-26), and high (\>26) disease activity. The SDAI score ranges from 0 to 86 where higher scores indicates high disease activity. SDAI score of \<=3.3 indicates LDA. Percentage of participants with SDAI \<=3.3 is presented in this outcome measure.
Percentage of Participants in Remission According to CDAI<=2.8 Baseline, Month 1, 3, 6, 12 18, and 24 CDAI is a composite end point, calculated as TJC + SJC (both using 28 joints) + PtGA (0-10 cm scale) + PhGA (0-10 cm scale). The CDAI score is classified into four categories: remission (\<=2.8), low (\>2.8-10), moderate (\>10-22), and high (\>22) disease activity. The CDAI score ranges from 0 to 76, where higher scores indicates high disease activity. CDAI score of \<=2.8 indicates LDA. Percentage of participants with CDAI \<=2.8 is presented in this outcome measure.
Percentage of Participants With Remission According to American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) 2011 Boolean Criteria Baseline, Month 1, 3, 6, 12 18, and 24 ACREULAR 2011 Boolean criteria is derived as: ACR Remission = 1, if SJC (using 28 joints) \<=1, TJC (using 28 joints) \<=1, CRP \<=1 mg/dL, and PtGA (0 to 10 cm scale, higher score=more disease activity) \<=1 centimeter (cm) otherwise ACR remission =0. Higher scores indicated greater affection due to disease activity. Percentage of participants with remission according to ACR-EULAR 2011 Boolean criteria is reported in this outcome measure.
Change From Baseline in DAS28-4 ESR Score at Month 1, 3, 6, 12, 18 and 24 Baseline, Month 1, 3, 6, 12, 18, and 24 DAS28-4 ESR is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). Components includes: TJC with 28 joints assessed, SJC with 28 joints assessed, ESR (mm/h) and PtGA recorded on 100 mm VAS (scores ranging 0 \[no disease activity\] to 100 mm \[maximum disease activity\], higher scores=more disease activity). The calculation of DAS28-4 ESR is as follows: 0.56 \* sqrt (TJC) + 0.28 \* sqrt (SJC) + 0.70\* In(ESR) + 0.014\* (PtGA); where ln = natural logarithm. Total DAS28-4 score range: 0 to 9.4, higher score=more disease activity. Mean change from baseline in DAS28-4 ESR score at months 3, 6, 12, 18 and 24 is presented in this outcome measure.
Change From Baseline in DAS28-4 CRP Score at Month 1, 3, 6, 12, 18 and 24 Baseline, Month 1, 3, 6, 12, 18, and 24 DAS28-4 CRP is a composite endpoint, calculated using 4 variables (represented by '-4' in the name). Components includes: TJC with 28 joints assessed, SJC with 28 joints assessed, CRP (mg/L) and PtGA recorded on 100 mm VAS (scores ranging 0 \[no disease activity\] to 100 mm \[maximum disease activity\], higher scores=more disease activity). The calculation of DAS28-4 CRP is as follows: 0.56 \* sqrt (TJC) + 0.28 \* sqrt (SJC) + 0.36 \* ln (CRP+l) + 0.014\*PtGA + 0.96; where ln = natural logarithm. Total DAS28-4 score range: 0 to 9.4, higher score=more disease activity. Mean change from baseline in DAS28-4 CRP score at months 3, 6, 12, 18 and 24 is presented in this outcome measure.
Number of Participants Responding To Treatment by Considering DAS28 (EULAR Criterion) Month 1, 3, 6, 12, 18, and 24 28 EULAR criteria to evaluate participant's response to treatment is categorised as good responder, moderate responder and non-responder based on participants DAS28-4 CRP score and decrease in DAS28-4 CRP compared to initial pre-treatment visit (Visit 0 \[V0\]). Good response: DAS28 at treatment visit \<= 3.2 and decrease in DAS 28 compared to V0 \>1.2. Moderate responder: DAS28 at treatment visit \> 3.2 to \<= 5.1 or \> 5.1 and decrease in DAS 28 compared to V0 \>1.2 DAS28 at treatment visit \<= 3.2 or \> 3.2 to \<= 5.1 and decrease in DAS 28 compared to V0 \>0.6 and \<=1.2. Non-responder: DAS28 at treatment visit \> 5.1 and decrease in DAS 28 compared to V0 \>0.6 to \<=1.2 DAS28 at treatment visit \<= 3.2 or \> 3.2 to \<= 5.1 or \> 5.1 and decrease in DAS 28 compared to V0 \<=0.6. Number of participants responding to treatment by considering DAS28 (EULAR criterion) is reported in this outcome measure.
Change From Baseline in TJC at Month 1, 3, 6, 12, 18 and 24 Baseline, Month 1, 3, 6, 12, 18, and 24 TJC (28) is the count of the total number of tender joints out of a possible 28 joints which are checked at the visit. TJC was used to measure the pain and inflammation in the joints. Mean change from baseline in TJC is reported in this outcome measure.
Change From Baseline in SJC at Month 1, 3, 6, 12, 18 and 24 Baseline, Month 1, 3, 6, 12, 18, and 24 SJC (28) is the count of the total number of swollen joints out of a possible 28 joints which are checked at the visit. SJC was used to measure the pain and inflammation in the joints. Mean change from baseline in TJC is reported in this outcome measure.
Number of Participants With Fibromyalgia Rapid Screening Tool (FiRST) Questionnaire Response Baseline, Month 1, 3, 6, 12, 18 and 24 FiRST is used to detect fibromyalgia in participants with diffuse rheumatic pain. It is a questionnaire which contains 6 items: diffuse pain, painful symptoms, fatigue, sleep and cognitive disorders, nonpainful abnormal sensations and functional somatic symptoms. Each of the 6 items contain yes or no response, and a positive answer to 5 out of the 6 answers can detect fibromyalgia. At each specified time points number of participants with "Yes" or "No" to fibromyalgia is reported in this outcome measure.
Change From Baseline in Duration of Morning Stiffness at Month 1, 3, 6, 12, 18 and 24 Baseline, Month 1, 3, 6, 12, 18 and 24 Morning stiffness is a common symptom of rheumatoid arthritis. The duration of morning stiffness is measured in minutes. Mean change from baseline in morning stiffness is reported in this outcome measure.
Number of Participants Based on Response to Girerd Questionnaire at Month 1, 3, 6, 12, 18 and 24 Month 1, 3, 6, 12, 18 and 24 Girerd questionnaire is used to evaluate participant's treatment compliance and is made up of 6 yes or no questions. lf the participant responds "no" to all questions, it is considered as participant is a good complier. lf the participant responds "yes" once or twice, it is considered as participant is a minor complier. lf the participant responds "yes" three times or more, it is considered as participant is a no-complier.
Change From Baseline in European Quality of Life (EuroQoL) 5-Dimension 3 Levels of Severity (EQ-5D-3L) Index Score at Month 1, 3, 6, 12, 18 and 24 Baseline, Month 1, 3, 6, 12, 18 and 24 EQ-5D-3L is a standardized, participant administered measure of self-reported instrument used to evaluate health-related quality of life. It consists of two parts: EQ-5D index score (Part I) and the EQ-VAS (Part II). For Part I, i.e. EQ-5D-3L index score, participants rated their current health state on 5 single-item dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression with each dimension having three levels of function:. 1=no problems, 2=some problems and 3=extreme problems. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score was transformed and results in a total index score range of 0 to 1.00; higher scores indicating a better health condition. Mean change from baseline in EQ-5D-3L index score is reported in this outcome measure.
Change From Baseline in Short Form-12 Health Survey (SF-12) Score at Month 1, 3, 6, 12, 18 and 24 Baseline, Month 1, 3, 6, 12, 18 and 24 SF-12 was a participant reported outcome survey that represented overall health status by measuring 8 health-related aspects of an individual: Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE) and Mental Health (MH). The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Responses on the SF-12 were also used to calculate 2 summary scores: Physical component score (PCS) and mental component score (MCS). The score range for each of these 2 summary scores was from 0 (poor health) to 100 (better health), where 100 indicated good health condition. Mean change from baseline in PCS and MCS scores are reported in this outcome measure.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score at Month 1, 3, 6, 12, 18 and 24 Baseline, Month 1, 3, 6, 12, 18 and 24 FACIT-Fatigue questionnaire consists of 13 self-evaluated questions. Each question has a response of values 0 (not at all) to 4 (very much). Score for each question is calculated by first reversing negatively stated-items (subtracting the response from '4' except for the 2 positively stated-items) and then summing the raw (0-4) scores. The FACIT-Fatigue total score is derived by summing the response to each question which gives a value between 0 (worse score) and 52 (best score). Higher scores represent better participant's status (less fatigue). Mean change from baseline in FACIT-Fatigue total score is reported in this outcome measure.
Number of Participants With Tofacitinib Tolerance Issue Month 24 Number of participants who discontinued tofacitinib due to tolerance issue.
Trial Locations
- Locations (52)
Cabinet Medical
🇫🇷Vincennes, France
Centre Hospitalier D Auxerre
🇫🇷Auxerre, France
Institut Calot Helio Marin
🇫🇷Berck Sur Mer, France
Centre Hospitalier de Fleyriat
🇫🇷Bourg en Bresse, France
Centre Hospitalier Departemental Vendee Les Oudairies
🇫🇷La Roche Sur Yon, France
Hopital Pierre Nouveau
🇫🇷Cannes, France
Hopital Gabriel Montpied
🇫🇷Clermont Ferrand, France
Centre Hospitalier de Compiegne
🇫🇷Compiegne, France
Hopital Victor Jousselin
🇫🇷Dreux, France
Centre Hospitalier des Deux Vallees Juvisy
🇫🇷Juvisy sur orge, France
Hopital Suburbain Du Bouscat
🇫🇷Le Bouscat, France
Hopital Suburbain
🇫🇷Le Bouscat, France
Hopital B Roger Salengro-chu De Lille
🇫🇷Lille Cedex, France
Hopital Dupuytren
🇫🇷Limoges, France
Clinique du Pont de Chaume
🇫🇷Montauban, France
Centre Hospitalier Montceau Les Mines-Hopital Jean Bouveri
🇫🇷Montceau Les Mines, France
Hopital Jacques Monod
🇫🇷Montivilliers, France
Clinique Beau Soleil
🇫🇷Montpellier, France
Hopital Lapeyronie
🇫🇷Montpellier, France
Hopital Caremeau
🇫🇷Nimes, France
Hopital Inter-armees Begin
🇫🇷Saint Mande, France
Centre Hospitalier Universitaire Saint Pierre
🇫🇷Saint Pierre, France
Centre Hospitalier de Bigorre Site La Gespe
🇫🇷Tarbes, France
hopital Avicenne
🇫🇷Bobigny, France
Infirmerie Protestante de Lyon
🇫🇷Caluire et Cuire, France
Centre Hospitalier Jean Rougier
🇫🇷Cahors, France
Centre Hospitalier de Montauban
🇫🇷Montauban, France
Cabinet Medical Saint Roch
🇫🇷Montpellier, France
Centre Hospitalier Pitie Salpetriere
🇫🇷Paris, France
Centre Hospitalier Orleans-Hopital La Source
🇫🇷Orleans, France
Centre Hospitalier Universitaire Saint Etienne Hopital Nord
🇫🇷Saint Priest En Jarez, France
Hopital Nord
🇫🇷Saint Priest en Jarez, France
Hopital des Hauts Clos
🇫🇷Troyes, France
Hopital Psv
🇫🇷Villeneuve Sur Lot, France
Clinique Medipole Garonne
🇫🇷Toulouse, France
Hopital Purpan
🇫🇷Toulouse, France
Cabinet de Rhumatologie
🇫🇷Tours, France
Centre Hospitalier D'arras
🇫🇷Arras Cedex, France
Hopital Robert Ballanger
🇫🇷Aulnay Sous Bois, France
Hopital Jacques CÅ“ur
🇫🇷Bourges, France
Centre Hospitalier de Carcassonne
🇫🇷Carcassonne, France
Hopital Henri Mondor
🇫🇷Creteil, France
Centre Hospitalier Universitaire de Lille - Hopital B Roger Salengro
🇫🇷Lille, France
Clinique de la Sauvegarde
🇫🇷Lyon Cedex 09, France
Clinique de La Sauvegarde / Cabinet Le Trait D Union
🇫🇷Lyon, France
Centre Hospitalier de Perigueux
🇫🇷Perigueux, France
Hospices Civils de Lyon - Hopital Lyon Sud- Hematologie
🇫🇷Pierre Benite Cedex, France
Centre Hospitalier La Miletrie
🇫🇷Poitiers, France
Centre Hospitalier Annecy Genevois Site Annecy
🇫🇷Pringy, France
Hopital Charles Nicolle
🇫🇷Rouen, France
Hopital Cochin
🇫🇷Paris, France
Hopital Bichat Claude Bernard
🇫🇷Paris, France