Persistence and factors associated with persistence to MTX in patients with RA.
| Persistence with MTX | |||||
|---|---|---|---|---|---|
| Study | Receiving MTX, n | Measurement | Cumulative Survival | No. Discontinuers, Reasons for Discontinuation | Factors Associated with Retention |
| Prospective studies by publication yr | |||||
| Alarcón, et al28 | 152 | Chart data/patient self-report | 1 yr: 71%, 3 yrs: 56%, 5 yrs: 50%, 6 yrs: 49%, 10 yrs: 30% | n = 78, tolerability 60%, inefficacy 8%, elective surgical procedure 8%, other 24% | (−) Major toxic event (−) Started MTX before 1984 |
| Alarcón, et al29 | n = 94, tolerability 53%, inefficacy 6%, elective surgical procedure 7%, other 33% | ||||
| Wolfe, et al30 | 187 | Chart data | Median 4.25 yrs | NR | (−) Reduced grip strength |
| Salaffi, et al34 | 51 | Chart data | 1 yr: 80%, 2 yrs: 75%, 3 yrs: 71% | n = 15, tolerability 53%, inefficacy 27%, elective surgical procedure 7%, poor compliance 13% | NR |
| De La Mata, et al35 | 152 | Chart data | Median 4.26 yrs, 95% CI 2.09–6.41 | n = 51a, tolerability 37%, inefficacy 43%, other 20% | None identified |
| Papadopoulos, et al41 | 212 | Chart data | 5 yrs: 55% Median 10 yrs | n = NR, tolerabilityb, inefficacyc | NR |
| Wolfe, et al43 | 675 | Patient report | Median 1.17 yrs, 95% CI 1.0–1.5 | NR | NR |
| Lie, et al47 | 1218 | Chart data | 6 mos: 83%, 2 yrs: 66% | n = NR at 6 mosd, tolerability 47%, inefficacy 30% n = NR at 6–12 mos, tolerability 27%, inefficacy 53% | (−) Younger age (−) Longer disease duration (−) Worse function (−) Worse patient’s global assessment |
| Lie, et al48 | 927 | Chart data | 1 yr: 75%, 2 yrs: 66%, 3 yrs: 58% | n = 446, tolerability 32%, inefficacy 45%, other 23% | NR |
| Gibofsky, et al53 | 1893 | Chart data | < 5 yrs: 82.7% (ETN + MTX) < 5 yrs: 84.9% (ETN + MTX + other DMARD) | n = 316, tolerability 25%, inefficacy 6%, cost 2%, patient decision 41%, other/unknown 27% | NR |
| Retrospective studies by publication yr | |||||
| Scully, et al31 | 124 | Chart data | 5 yrs: 31% | n = 85, tolerability 52%, inefficacy 24%, concurrent illness 11%, personal reasons 8%, lost to followup 6% | (+) Younger age (+) Shorter duration of disease |
| Tishler, et al32 | 126 | Chart data | 2 yrs: 72%, 3 yrs: 72%, 4 yrs: 67%, 5 yrs: 56%, 7 yrs: 56% Mean 3.07 ± 1.53 yrs | n = 40, tolerability 68%, inefficacy 25%, poor compliance/fear of toxicity 8% | (+) Seronegativity |
| McKendry and Dale33 | 144 | Chart data | 2 yrs: 53%, 5 yrs: 25% | n = 81, tolerability 53%, inefficacy 22%, other medical reasons 10%, nonmedical reasons 6%, lost to followup 9% | NR |
| Buchbinder, et al37 | 587 | Chart data | 1 yr: 87%, 2 yrs: 82%, 5.8 yrs: 76% | n = NR, tolerability 16%e, inefficacy 8%e | (−) Age ≥ 65 yrs, for discontinuation due to toxicity Treating rheumatologist |
| Keysser, et al36 | 371 | Chart data | 4.6 yrs: 40% | n = 224, tolerability 26%, inefficacy 72%, other 2% | NR |
| Wluka, et al38 | 392 | Chart data | 12 yrs: 53% | n = 187, tolerability 45%, inefficacy 22%, remission 12%, other 13%, unknown 8% | (−) Age ≥ 65 yrs |
| Ortendahl, et al39 | 437 | Chart data | 2.5 yrs: 59% 5 yrs: 49% Median 4.33 yrs | NR | (+) Shorter disease duration (−) Fewer previous NSAID (−) Fewer previous DMARD |
| Aletaha and Smolen40 | 389 | Chart data | 5 yrs: 37% (≤ 10 mg/week), 57% (≥ 12.5 mg/week), median 3.33 yrs, IQR 1–9.42 | NR | (+) Higher dose MTX |
| Hoekstra, et al42 | 1022 | Chart data | 5 yrs: 64%, 9 yrs: 50% | n = 394a, tolerability 45%, inefficacy 18%, remission 5%, patient’s request 7%, other 24% | (+) Folic acid supplementation (+) Concurrent prednisone Attending rheumatologist |
| Yazici, et al44 | 248 | Chart data | 5 yrs: 79% | n = 46, tolerability 57%, inefficacy 33%, disease improved 7%, other diseases 2%, pregnancy 2% | NR |
| Kapral, et al49 | 86 | Chart data | Mean 2 ± 0.23 yrs | n = 79, tolerability 23%, inefficacy 47% | (+) Previous MTX use |
| Ideguchi, et al45 | 273 | Chart data | 3 yrs: 80%, 5 yrs: 62% | n = 43, tolerability 79%, inefficacy 14%, remission 5%, patient’s request 2% | (+) Fewer previous DMARD |
| Bernatsky and Ehrmann Feldman50 | 246 | Claims data | 6 mos: 80% 1 yr: 68% 2 yrs: 50% | NR | (−) Age > 70 yrs (−) Higher comorbidity score (−) IM MTX vs PO MTX |
| Agarwal, et al46 | 66 | Chart data/patient self-report | Median 2.33 yrs, IQR 1.25–3.75 | NR | (+) First-line treatment with MTX (+) MTX monotherapy |
| Scott, et al51 | 198 | Chart data | 6 mos: 78% | n = 43, tolerability 56%, inefficacy 14% | NR |
| Curtis, et al52 | 24,479 | Claims data | 1 yr: 50% | NR | NR |
| Nikiphorou, et al54 | 762 | Chart data | Median 0.83 yrs, range 0.02–10, in discontinuers | n = 260, tolerability 78%, inefficacy 12%, no longer indicated 7%, patient’s choice 5%, not stated 5% | NR |
| Bliddal, et al55 | 18,703 | Claims data | Median 6.15 yrsf | NR | (−) Female sex (−) Younger age (−) Longer time between RA diagnosis and initiation of MTX (−) Comorbidities: heart failure, atherosclerosis, mild liver disease, kidney disease |
| Branco, et al56 | 50 | Chart data | 1 yr: 93.9%g, 2 yrs: 91.5%g, 3 yrs: 76.8%g | n = 9, tolerability 67%, inefficacy 22%, other 11% | NR |
↵a No. treatment episodes discontinued, not no. discontinuers.
↵b Twenty-two MTX prescriptions were discontinued because of side effects; total nos. patients discontinuing MTX and prescription discontinuations are not stated.
↵c Main reason for discontinuation; additional detail not provided.
↵d Seventeen percent of patients discontinued MTX during the first 6 months.
↵e Sixteen percent of all patients discontinued MTX because of intolerability; 8% of all patients discontinued MTX because of lack of efficacy.
↵f Persistence on MTX ≥ 7.5 mg/week (defined by the authors as the minimal effective dose).
↵g Extrapolated, owing to short followup duration and low actual withdrawal rate. MTX: methotrexate; RA: rheumatoid arthritis; ETN: etanercept; DMARD: disease-modifying antirheumatic drugs; NR: not reported; NSAID: nonsteroidal antiinflammatory drugs; IM: intramuscularly; PO: by mouth; IQR: interquartile range.