Takaisin

Upadacitinib treatment in patients with active psoriatic arthritis: effectiveness and safety compared to placebo.

Näytönastekatsaukset
Krista Nuotio
10.11.2021

Level of evidence: A

Oral upadacitinib treatment at the dose of 15 mg daily increases the proportion of patients with active psoriatic arthritis achieving the ACR20 response at week 12, when compared to placebo (approximately 57–71 % vs. 24–36 %, depending on patient population).

Significantly higher ACR50 and ACR70 response rates were observed for upadacitinib compared to placebo at week 12, but the effect was seen more slowly. There were more adverse events with both doses of upadacitinib than with placebo and more serious adverse events with the 30 mg dose of upadacitinib, but no new safety signals were identified compared with what has been observed with upadacitinib in rheumatoid arthritis «Cohen SB, van Vollenhoven RF, Winthrop KL ym. Safe...»3. The rates of serious infections, herpes zoster, creatine phosphokinase elevations and neutropaenia were higher for the 30 mg dose than for the 15 mg dose. Rates of deaths and malignancies with upadacitinib appeared consistent with expected rates from the general population «Cohen SB, van Vollenhoven RF, Winthrop KL ym. Safe...»3. The quality and applicability of the evidence are good.

Table 1. Description of the included studies
Reference Study type Population Intervention and comparison Outcomes Risk of bias
RCT=randomized controlled trial, pts=patients, PsA=Psoriatic arthritis, UPA=upadacitinib, PBO= placebo, ADA=adalimumab, DMARD=disease-modifying antirheumatic drug, ACR20/50/70=American College of Rheumatology (ACR) 20 response, HAQ-DI=Health Assessment Questionnaire-Disability Index, sIGA=Static Investigator Global Assessment, PASI75=Psoriasis Area Severity Index, mTSS=modified total Sharp–van der Heijde Score, MDA=minimal disease activity, resolution of enthesitis, noninferiority of UPA vs. ADA, SF-36=Short Form Health Survey questionnaire, PCS= Physical Component Summary, FACIT-F=Functional Assessment of Chronic Illness Therapy-Fatigue score, superiority of UPA vs. ADA, resolution of dactylitis, pain, SAPS=Self-Assessment of Psoriasis Symptoms.
«McInnes IB, Anderson JK, Magrey M ym. Trial of Upa...»1 RCT phase III multicenter study. 1704 pts ≥ 18 years with active PsA and had a historical or current plaque psoriasis, and an
inadequate response or unacceptable side effects
with at least one nonbiologic DMARD.
(N=1281 patients if ADA is excluded.)
Oral UPA 15 mg, oral UPA 30 mg, PBO and s.c. ADA. Primary: ACR20 response at week 12
Secondary: HAQ-DI, sIGA, PASI75, mTSS, MDA, resolution of enthesitis, noninferiority of UPA vs. ADA, SF-36, FACIT-F, superiority of UPA vs. ADA, resolution of dactylitis, pain, SAPS.
Low
«Mease PJ, Lertratanakul A, Anderson JK ym. Upadaci...»2 RCT phase III multicenter study. 642 pts ≥ 18 yrs with active PsA and prior inadequate response or intolerance to at least one biologic DMARD. Oral UPA 15 mg, oral UPA 30 mg or PBO at week 12 Primary: ACR20 response at week 12
Secondary:
ACR20 at week 2; ACR50, ACR70, HAQ-DI, FACIT-F, SF-36 and PCS at week 12; sIGA, PASI75 and SAPS at week 16; MDA at week 24.
Low
Table 2. Additional comments for included studies
Reference Comments
«McInnes IB, Anderson JK, Magrey M ym. Trial of Upa...»1 Study was funded by AbbVie.
The extension period is ongoing, with up to 3 years.
«Mease PJ, Lertratanakul A, Anderson JK ym. Upadaci...»2 Study was funded by AbbVie.

Results

Table 3. ACR20 response at week 12
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 (95% CI)
I=intervention; C=comparison; CI=confidence interval, UPA=upadacitinib, ADA=adalimumab, PBO= placebo, NA=not applicable
«McInnes IB, Anderson JK, Magrey M ym. Trial of Upa...»1 1704 pts (n=429 UPA 15mg, n=423 UPA 30mg, n=423 PBO, n=429 ADA) 12 weeks, efficacy and safety up to 24 weeks. 15 mg UPA
70.6 %
30 mg UPA
78.5%
36.2 % 34.5 % (28.2–40.7)
42.3 % (36.3–48.3)
«Mease PJ, Lertratanakul A, Anderson JK ym. Upadaci...»2 642 pts (n= 211 UPA 15 mg, n= 218 UPA 30mg and n= 212 PBO) 12 weeks, long-term efficacy and safety up to 24 weeks. 15 mg UPA
56.9 %
30 mg UPA
63.8 %
24.1 % 32.8 % (24.0–41.6)
39.7 % (31.1–48.3)
Level of evidence: high
Table 4. ACR50 response at week 12
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 (95% CI)
I=intervention; C=comparison; CI=confidence interval, UPA=upadacitinib, ADA=adalimumab, PBO= placebo, NA=not applicable
«McInnes IB, Anderson JK, Magrey M ym. Trial of Upa...»1 1704 pts (n=429 UPA 15mg, n=423 UPA 30mg, n=423 PBO, n=429 ADA) 12 weeks, efficacy 15 mg UPA
37.5 %
30 mg UPA
51.8 %
13.2 % 24.3 % (18.7–29.9)
38.6 % (32.8–44.3)
«Mease PJ, Lertratanakul A, Anderson JK ym. Upadaci...»2 642 pts (n= 211 UPA 15 mg, n= 218 UPA 30mg and n= 212 PBO) 12 weeks, efficacy 15 mg UPA
31.8 %
30 mg UPA
37.6 %
4.7 %
27.1 % (20.1–33.9)
32.9 % (25.9–39.9)
Level of evidence: high
Table 5. ACR70 response at week 12
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 (95% CI)
I=intervention; C=comparison; CI=confidence interval, UPA=upadacitinib, ADA=adalimumab, PBO= placebo, NA=not applicable
«McInnes IB, Anderson JK, Magrey M ym. Trial of Upa...»1 1704 pts (n=429 UPA 15mg, n=423 UPA 30mg, n=423 PBO, n=429 ADA) 12 weeks, efficacy 15 mg UPA
15.6 %
30 mg UPA
25.3 %
2.4 %
13.2 % (9.5–17.0)
22.9 % (18.5–27.3)
«Mease PJ, Lertratanakul A, Anderson JK ym. Upadaci...»2 642 pts (n= 211 UPA 15 mg, n= 218 UPA 30mg and n= 212 PBO) 12 weeks, efficacy 15 mg UPA
8.5 %
30 mg UPA
16.5 %
0.5% 8.0 % (4.2–11.9)
16.0 % (11.0–21.1)
Level of evidence: high
Table 6. All adverse events at week 12
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 (95% CI)
I=intervention; C=comparison; CI=confidence interval, UPA=upadacitinib, ADA=adalimumab, PBO= placebo, NA=not applicable
«McInnes IB, Anderson JK, Magrey M ym. Trial of Upa...»1 1704 pts (n=429 UPA 15mg, n=423 UPA 30mg, n=423 PBO, n=429 ADA) 24 weeks 15 mg UPA
66.9 %
30 mg UPA
72.3 %
59.6 %
«Mease PJ, Lertratanakul A, Anderson JK ym. Upadaci...»2 642 pts (n= 211 UPA 15 mg, n= 218 UPA 30mg and n= 212 PBO) 24 weeks 15 mg UPA
64.0 %
30 mg UPA
78.0 %
65.6 %
Level of evidence: moderate
The quality of evidence is downgraded due to short follow-up.
Table 7. All adverse events at week 52
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 (95% CI)
I=intervention; C=comparison; CI=confidence interval, UPA=upadacitinib, ADA=adalimumab, PBO= placebo, NA=not applicable
«McInnes IB, Anderson JK, Magrey M ym. Trial of Upa...»1 1704 pts (n=429 UPA 15mg, n=423 UPA 30mg, n=423 PBO, n=429 ADA) 12 weeks, efficacy and safety up to 24 weeks. 15 mg UPA
70.6 %
30 mg UPA
78.5 %
36.2 % 34.5 % (28.2–40.7)
42.3 % (36.3–48.3)
Level of evidence: moderate

References

  1. McInnes IB, Anderson JK, Magrey M ym. Trial of Upadacitinib and Adalimumab for Psoriatic Arthritis. N Engl J Med 2021;384:1227-1239 «PMID: 33789011»PubMed
  2. Mease PJ, Lertratanakul A, Anderson JK ym. Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. Ann Rheum Dis 2020;: «PMID: 33272960»PubMed
  3. Cohen SB, van Vollenhoven RF, Winthrop KL ym. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis 2020;: «PMID: 33115760»PubMed