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Time until onset of action when treating psoriatic arthritis: meta-analysis and novel approach of generating confidence intervals

  • Phuong Anh Pham
  • Corinna DresslerEmail author
  • Lisa Eisert
  • Alexander Nast
  • Ricardo Niklas Werner
Systematic Review
  • 156 Downloads

Abstract

Psoriatic arthritis (PsA) is associated with progressive joint destruction and reduced quality of life. The time until a drug treatment starts to show an effect (TOA) is important for preventing joint destruction. The objective was to assess the time until onset of action of drugs when treating PsA. A systematic review of PsA drug trials was performed. Outcomes were: time until 25% of patients (TOA) reached (1) ≥ 20%, (2) ≥ 50% improvement in modified American College of Rheumatology response criteria (ACR), (3) ≥ 75% reduction in Psoriasis Area and Severity Index (PASI75). 95% confidence intervals were calculated extracting data from graphs using a novel method. Meta-analysis was conducted. Two head-to-head trials show no difference between ixekizumab and adalimumab or adalimumab and tofacitinib for TOA-ACR outcomes. For PASI75, ixekizumab had a faster onset than adalimumab. Infliximab plus MTX was faster than MTX alone. Pooled results from 32 study arms for TOA-ACR20 (week [95% CI]) are: < 2 weeks: infliximab (1.18 [0.72–1.65]), ixekizumab (1.04 [0.80–1.28]), tofacitinib (10 mg 1.56 [1.14–1.98]); ≤ 4 weeks: adalimumab (1.95 [1.35–2.55]), secukinumab (75 mg 1.89 [0.16–3.62], 150 mg 2.13 [1.34–2.91], 300 mg 2.26 [1.75–2.76]), tofacitinib (5 mg 2.20 [1.41–2.99]); 4 + weeks: apremilast, ustekinumab. For TOA-ACR50, all pooled point estimates are > 4 weeks. For TOA-PASI75, the range is between 2.24 [1.65–2.84] for ixekizumab and 6.03 [3.76–8.29] for adalimumab. Indirect, mixed comparison suggest a faster onset of infliximab, ixekizumab and tofacitinib compared to apremilast, methotrexate and ustekinumab for ACR20, not ACR50. For PASI75, ixekizumab is faster than adalimumab.

Keywords

Arthritis Psoriatic [MeSH] Anti-rheumatic agents* Meta-analysis [MeSH] Confidence intervals [MeSH] 

Abbreviations

ACR

American College of Rheumatology

ACR20

≥ 20% improvement in modified American College of Rheumatology response criteria

ACR50

≥ 50% improvement in modified American College of Rheumatology response criteria

ADA

Adalimumab

APR

Apremilast

bDMARD

Biological disease-modifying anti-rheumatic drug

BID

Twice a day

BIW

Twice weekly

BW

Body weight

CASPAR

Classification criteria for the diagnosis of psoriatic arthritis

CI

Confidence intervals

CRP

C-reactive protein

CSA

Cyclosporine

csDMARD

Conventional synthetic disease-modifying anti-rheumatic drug

CZP

Certolizumab pegol

d

Day

EE

Early escape

ES

Point estimate

ESR

Erythrocyte sedimentation rate

ETA

Etanercept

EULAR

European League against Rheumatism

GOL

Golimumab

GRAPPA

Group for research and assessment of psoriasis and psoriatic arthritis

GUS

Guselkumab

Hx

History of

ICTRP

The International Clinical Trials Registry Platform

INF

Infliximab

IQR

Interquartile range

iv

Intravenous

IXE

Ixekizumab

LE

Lesion

LEF

Leflunomide

LES

Least squares

MTX

Methotrexate

NA

Not available

NI

No information

NR

Not restricted

NSAID

Non-steroidal anti-inflammatory drug

PASI

Psoriasis Area and Severity Index

PASI75

≥ 75% reduction in Psoriasis Area and Severity Index

PBO

Placebo

PGA

Physician’s global assessment

PICOS

Participants, interventions, comparisons, outcomes, study design

PJC

Painful joint count

PRED

Prednisolone

PRISMA

Preferred reporting items for systematic reviews and meta-analyses

PsA

Psoriatic arthritis

PsARC

Psoriatic arthritis response criteria

Pso

Cutaneous psoriasis

pts

Patients

Q12W

Every 12 weeks

Q1W

Once per week

Q2W

Every 2 weeks

Q4W

Every 4 weeks

QD

Once per day

RA

Rheumatoid arthritis

RF

Rheuma factor

sc

Subcutaneous

SD

Standard deviation

SE

Standard error

SEC

Secukinumab

SJC

Swollen joint count

SSZ

Sulfasalazine

tbc

Tuberculosis

TJC

Tender joint count

TOF

Tofacitinib

tsDMARD

Targeted synthetic disease-modifying anti-rheumatic drug

TOA

Time until onset of action

TOA-ACR20

Time until 25% of patients reach a ≥ 20% improvement in ACR criteria

TOA-ACR50

Time until 25% of patients reach a ≥ 50% improvement in ACR criteria

TOA-PASI75

Time until 25% of patients reach a ≥ 75% improvement in PASI

UST

Ustekinumab

w

Week/weeks

y/yrs

Year/years

Notes

Author contributions

PAP: design, data acquisition, analysis and interpretation, and drafting the manuscript. CD: design, data acquisition, analysis and interpretation. LE: design, data acquisition. AN: conception, design. RNW: conception, design and data interpretation. All authors have revised the manuscript critically for important intellectual content and approved the final manuscript. Furthermore, all authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. No external writing or editing support was involved.

Funding

The project was funded by Eli Lilly Germany. The funder had no role in the design, conduct, writing and editing of the project.

Compliance with ethical standards

Conflict of interest

Authors Phuong Anh Pham (PAP), Dr. Corinna Dressler (CD), Ricardo N. Werner, MD (RNW) declare that they have no conflicts of interest. Author Lisa Eisert, MD (LE) has received seminar participation fees from Pfizer (Enbrel), Leo Pharma (Daivobet, Protopic, Enstilar). Author Prof. Alexander Nast, MD (AN) has received institutional research grants/participated as an investigator (without personal honoraria) in research projects, advisory activities or trials from the following companies with an interest in psoriatic arthritis: Lilly, Novartis, Dermira. AN has received personal honoraria for lectures/educational activities from the following companies which—to his knowledge—currently have no interest in psoriatic arthritis: Bayer Healthcare, Pierre Fabre, Boehringer Ingelheim.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

296_2019_4244_MOESM1_ESM.docx (212 kb)
Supplementary material 1 (DOCX 213 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Evidence-Based Medicine (dEBM), Department of Dermatology, Venerology und Allergy, Berlin Institute of HealthCharité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu BerlinBerlinGermany

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