It may be, that treatment with apremilast causes more adverse events than placebo, but they are mostly mild, and severe adverse events may not be common.
| Ref. | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| MA=meta-analysis, RCT=randomized controlled trial. ARC20=20% improvement in signs and symptoms of psoriatic arthritis according to American College of Rheumatology criteria, APR=apremilast | |||||
| «Ramiro S, Smolen JS, Landewé R ym. Pharmacological...»1 | MA | 2686 adult (≥ 18) patients with clinical diagnosis of psoriatic arthritis. Previously inadequate response to standard therapies or TNFi-failure. | APR 30 or 20 mg twice daily vs. placebo | Primary: ACR20 and adverse events at week 16; Secondary: ACR50, ACR70, and PASI50-75-90 at week 16, serious adverse events |
Moderate |
| «Strand V, Elaine Husni M, Betts KA ym. Network met...»2 | Network MA | 2686 adult (≥ 18) patients with active psoriatic arthritis. | APR 30 or 20 mg twice daily vs. placebo | Primary ACR20 at week 24 and PASi75-90. | Moderate |
| «Nash P, Ohson K, Walsh J ym. Early and sustained e...»3 | RCT | biological-naive patients with active psoriatic arthritis | APR 30 mg twice daily vs. placebo | Primary: ACR20 and adverse events at week 16; Secondary: DAS-28ACR50, ACR70, and HAQ-DI, adverse events |
Moderate |
| «Mease PJ, Gladman DD, Gomez-Reino JJ ym. Long-Term...»4 | RCT (Pooled analysis of 3 RCTs) | 1493 adult (≥ 18) patients with active psoriatic arthritis. | APR 30 or 20 mg twice daily vs. placebo | Adverse events | Moderate |
| Reference | Comments |
|---|---|
| APR=apremilast | |
| «Ramiro S, Smolen JS, Landewé R ym. Pharmacological...»1 | Systematic review and meta-analysis. At the time of the analysis only 1 study had been published as full text article (PALACE-1), the others as abstracts (PALACE 2-4). PALACE 1 risk of bias moderate due to only per-protocol analysis, unclear sequence generation and allocation concealment. |
| «Strand V, Elaine Husni M, Betts KA ym. Network met...»2 | The network analysis is based on same studies as meta-analysis [1]. Risk of bias assessment is not reported. Risk of bias is moderate due to unclear sequence generation and allocation concealment. Sponsored by Celgene Corporation. |
| «Nash P, Ohson K, Walsh J ym. Early and sustained e...»3 | Phase IIIb RCT. Patients had to discontinue their csDMARD at least 1 day before baseline assessment. Patients were eligible for early escape at week 16 if no improvement by >10% in swollen joint count and tender joint count. At week 24 placebo group switched to apremilast. 84.5% completed week 24. |
| «Mease PJ, Gladman DD, Gomez-Reino JJ ym. Long-Term...»4 | Randomization in 3 groups (APR 30 mg, APR 20 mg, placebo) lasted for 24 weeks. Thereafter, placebo patients were randomized to receive APR 30 or 20 mg up to 54 weeks. After 54 weeks, patients continued on medication and were followed up to 156 weeks. Here, the results on placebo controlled phase (24 weeks) are presented. |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time, weeks | Absolute number of events (%) I | Absolute number of events (%) C | Risk Ratio and NNT vs. placebo (95 % CI) |
|---|---|---|---|---|---|
| I= intervention; C=comparison; CI=confidence interval, NNT=number needed to treat, APR=apremilast, NA=not available | |||||
| «Ramiro S, Smolen JS, Landewé R ym. Pharmacological...»1 | 4 RCTs APR 30 mg 1344 (672/672) APR 20 mg 1342 (675/667) |
16 | APR 30 mg: 247 (36.8 %) APR 20 mg: 215 (31.9 %) |
125 (18.6 %) 125 (18.7 %) |
RR 1.98 (1.64–2.38) NNT range 4.2–6.7 1.7 (1.4–2.06) NNT range 5.3–9.5 |
| «Strand V, Elaine Husni M, Betts KA ym. Network met...»2 | 4 RCTs (1347/1339) |
24 | 33.4% (95 % CI 27.1–40.4) | 17.0 (95 % CI 15.4-18.7) | NNT 6.1 (4.4–9.5) |
| «Nash P, Ohson K, Walsh J ym. Early and sustained e...»3 | 1 RCT 219 (110/109) |
16 | 42 (38.2 %) | 22 (20.2 %) | NA |
| Level of evidence: low The quality of evidence is downgraded due to study limitations. |
|||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Absolute difference vs. placebo (95% CI) |
|---|---|---|---|---|---|
| I= intervention; C=comparison; CI=confidence interval, NA=not available | |||||
| «Strand V, Elaine Husni M, Betts KA ym. Network met...»2 | 4 RCTs (1347/1339) |
24 weeks | 15.5 % (95 % CI 10.9–21.8) | 7.0 (95 % CI 5.9–8.2) | NNT 11.8 (7.0–23.5) |
| «Nash P, Ohson K, Walsh J ym. Early and sustained e...»3 | 1 RCT 219 (110/109) |
16 | 20 (18.2 %) | 5 (4.6 %) | NA |
| Level of evidence: low The quality of evidence is downgraded due to study limitations and imprecision (wide confidence interval). |
|||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Absolute difference vs. placebo (95% CI) |
|---|---|---|---|---|---|
| I=intervention; C=comparison; CI=confidence interval, NA=not available | |||||
| «Strand V, Elaine Husni M, Betts KA ym. Network met...»2 | 4 RCTs (1347/1339) |
24 weeks | 5.0(95 % CI 2.7–9.1) | 2.5 (95 % CI 1.9–3.3) | NNT 40.3 (15.8–222.7) |
| «Nash P, Ohson K, Walsh J ym. Early and sustained e...»3 | 1 RCT 219 (110/109) |
16 | 7 (6.4 %) | 0 (0 %) | NA |
| Level of evidence: low The quality of evidence is downgraded due to study limitations and imprecision (wide confidence interval). |
|||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time, weeks | Absolute number of events (%) I | Absolute number of events (%) C | Absolute difference vs. placebo (95% CI) |
|---|---|---|---|---|---|
| I=intervention; C=comparison; CI=confidence interval, APR=apremilast, NA=not available EAIR = exposure-adjusted incidence rate |
|||||
| «Ramiro S, Smolen JS, Landewé R ym. Pharmacological...»1 | 1 RCT APR 30 mg 351 (175/176) APR 20 mg 351 (175/176) |
16 | At least one AE APR 30 mg: (7%) APR 20 mg: (4.8%) |
At least one AE Placebo: (4.8%) |
NA |
| «Nash P, Ohson K, Walsh J ym. Early and sustained e...»3 | 1 RCT 219 (110/109) |
24 | Any AE 73 (67.9) Any serious AE 3 (2.8) |
Any AE 69 (63.3) Any serious AE 5 (4.6) |
NA |
| «Mease PJ, Gladman DD, Gomez-Reino JJ ym. Long-Term...»4 | 3 RCTs APR 30 mg N=497 APR 20 mg N=501 Placebo N=495 |
24 | Any AE EAIR/100 yrs APR 265.1 APR 30mg 272.0 APR 20mg 258.8 Serious AE EAIR/100 yrs APR 30mg 9.2 APR 20mg 8.0 |
Any EA EAIR/100 yrs Placebo 200.7 Serious AE EAIR/100 yrs Placebo 11.5 |
Any AE EAIR/100 yrs 64.4 Serious AE EAIR/100 yrs -2.9 |
| Level of evidence: low The quality of evidence is downgraded due to study limitations. |
|||||