Superiority of a Treat-to-Target Strategy over Conventional Treatment with Fixed csDMARD and Corticosteroids: A Multi-Center Randomized Controlled Trial in RA Patients with an Inadequate Response to Conventional Synthetic DMARDs, and New Therapy with Certolizumab Pegol
Abstract
:1. Introduction
2. Methods
2.1. Patients
2.2. Procedures
2.3. Therapeutic Strategies
2.3.1. T2T csDMARD Strategy
2.3.2. T2T GC Strategy
- Small joints: metacarpophalangeal (MCP), proximal interphalangeal (PIP), metatarsophalangeal joints (MTP): distal interphalangeal joints (DIP), sternoclavicular joint, acromioclavicular joint, tarsus, and distal interphalangeal joints of the feet (IP): 10 mg triamcinolone;
- Intermediate joints: carpus, elbow, ankle: 20 mg triamcinolone with 0.5 mL 1% lidocaine; big joints: knee, shoulder, hip: 40 mg triamcinolone with 4 mL 1% lidocaine.
2.3.3. Fixed Regimen Strategy
2.4. Primary Objective
2.5. Anti-Drug Antibodies
2.6. Data and Statistical Methods
2.6.1. Power Calculation
2.6.2. Statistical Analyses
3. Results
3.1. Patient Demographics/Characteristics
3.2. Clinical Responses
3.3. Patient-Related Outcomes
3.4. Adverse Events
3.5. Cumulative Steroid Dose
3.6. Therapeutic Changes of the csDMARD Protocol
3.7. ADA (Anti Drug Antibodies) Antibodies
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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T2T (n = 21) | Fixed Regimen (n = 22) | |
---|---|---|
Age (a, mean) | 56.3 ± 15.4 | 56.8 ± 14.8 |
Gender (% female) | 66.7% | 63.6% |
BMI (Kg/m2, mean) | 28.6 ± 4.4 | 28.7 ± 5.6 |
ACPA pos. (%) | 47.6% | 47.6% |
RF pos. (%) | 66.7% | 81.0% |
Erosive disease (%, defined by treating physician) | 26.3% | 30.0% |
Disease duration (a, median, range) | 0.99, 3 months–10 years | 0.85, 3 months–18 years |
Concomittant DMARD at baseline | MTX 10 mg/w, n = 2 MTX 15 mg/w, n = 9 MTX 20 mg/w, n = 4 MTX 25 mg/w, n = 3 Lef 20 mg/d, n = 3 | MTX 10 mg/w: n = 2 MTX 15 mg/w n = 6 MTX 20 mg/w n = 3 MTX 25 mg n = 5 MTX + HCQ, n = 2 15 mg/w + 200 mg/d; 20 mg/w + 400 mg/d SSZ n = 2 Lef n = 2 |
Concomitant GC (mean dose *, number of patients) | 4.7 mg/d; n = 8 | 6.3 mg/d; n = 10 |
Disease activity score (DAS 28) | 5.89 ± 0.98 | 6.16 ± 0.86 |
Tender joint score (0–68) | 20.7 ± 10.3 | 23.2 ± 13.7 |
Swollen joint score (0–66) | 18.9 ± 7.6 | 18.6 ± 10.9 |
Pain score (0–100) | 65.3 ± 20.8 | 60.2 ± 21.0 |
Patient global assessment | 70.1 ± 16.0 | 64.2 ± 16.9 |
Physician global assessment (0–100) | 71.8 ± 8.8 | 67.0 ± 19.0 |
C-reactive protein (mg/L) | 13.0 ± 16.2 | 17.1 ± 18.8 |
Erythrocyte sedimentation rate (mm/h) | 28.7 ± 19.9 | 35.1 ± 25.2 |
Health assessment questionnaire score * (0–3) | 0.84 ± 0.62 | 0.85 ± 0.64 |
T2T | Fixed Regimen | p-Value | |
---|---|---|---|
Patient’s pain score | −53.34 | −50.51 | n.s. |
Patient’s global assessment | −56.21 | −49.59 | n.s. |
Physician’s global assessment | −64.62 | −31.74 | <0.001 |
Tender joint count (68) | −19.67 | −9.9 | <0.001 |
Swollen joint count (66) | −17.89 | −8.76 | <0.001 |
ESR (mm/h) | −12.83 | −17.86 | <0.001 |
CRP (mg/L) | −3.03 | −7.64 | <0.001 |
HAQ-DI | −0.68 | −0.25 | n.s. |
CDAI | −33.81 | −21.9 | <0.001 |
Fixed Regimen | T2T | |
---|---|---|
Total (n) | 51 | 55 |
Patients with AEs (n) | 16 | 18 |
Intensity (mild/moderate/severe, n) | 49/1/1 | 50/4/1 |
SAE (n) | 1 * | 2 ** |
Related (Not, unlikely/possibly/ probably/definitely, n) | 22/3/21/4/1 | 33/3/19/0/1 |
Cardiovascular (n) | 2 | 7 |
Dermatological (n) | 6 | 4 |
Gastrointestinal (n) | 3 | 4 |
General (n) | 1 | 4 |
Hepatology (n) | 2 | 1 |
Infection | 10 | 13 |
Injection site reaction to CZP (n) | 4 | 3 |
Injury (n) | 5 | 2 |
Joint injection reaction (n) | - | 3 |
Musculoskeletal (n) | 4 | 3 |
Neurological (n) | 11 | 10 |
Ophthalmological (n) | 1 | 1 |
Psychology (n) | 2 | 1 |
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Mueller, R.B.; Spaeth, M.; von Restorff, C.; Ackermann, C.; Schulze-Koops, H.; von Kempis, J. Superiority of a Treat-to-Target Strategy over Conventional Treatment with Fixed csDMARD and Corticosteroids: A Multi-Center Randomized Controlled Trial in RA Patients with an Inadequate Response to Conventional Synthetic DMARDs, and New Therapy with Certolizumab Pegol. J. Clin. Med. 2019, 8, 302. https://doi.org/10.3390/jcm8030302
Mueller RB, Spaeth M, von Restorff C, Ackermann C, Schulze-Koops H, von Kempis J. Superiority of a Treat-to-Target Strategy over Conventional Treatment with Fixed csDMARD and Corticosteroids: A Multi-Center Randomized Controlled Trial in RA Patients with an Inadequate Response to Conventional Synthetic DMARDs, and New Therapy with Certolizumab Pegol. Journal of Clinical Medicine. 2019; 8(3):302. https://doi.org/10.3390/jcm8030302
Chicago/Turabian StyleMueller, Ruediger B., Michael Spaeth, Cord von Restorff, Christoph Ackermann, Hendrik Schulze-Koops, and Johannes von Kempis. 2019. "Superiority of a Treat-to-Target Strategy over Conventional Treatment with Fixed csDMARD and Corticosteroids: A Multi-Center Randomized Controlled Trial in RA Patients with an Inadequate Response to Conventional Synthetic DMARDs, and New Therapy with Certolizumab Pegol" Journal of Clinical Medicine 8, no. 3: 302. https://doi.org/10.3390/jcm8030302