Systematic literature review and network meta-analysis of therapies for psoriatic arthritis on patient-reported outcomes

Abstract

Objectives: Head-to-head clinical trials are common in psoriasis, but scarce in psoriatic arthritis (PsA), making treatment comparisons between therapeutic classes difficult. This study describes the relative effectiveness of targeted synthetic (ts) and biologic (b) disease-modifying antirheumatic drugs (DMARDs) on patient-reported outcomes (PROs) through network meta-analysis (NMA).

Design: A systematic literature review (SLR) was conducted in January 2020. Bayesian NMAs were conducted to compare treatments on Health Assessment Questionnaire Disability Index (HAQ-DI) and 36-item Short Form (SF-36) Health Survey including Mental Component Summary (MCS) and Physical Component Summary (PCS) scores.

Data sources: Ovid MEDLINE (including Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily),Embase and Cochrane Central Register of Controlled Trials.

Eligibility criteria: Phase III randomised controlled trials (RCTs) evaluating patients with PsA receiving tsDMARDS, bDMARDs or placebo were included in the SLR; there was no restriction on outcomes.

Data extraction and synthesis: Two independent researchers reviewed all citations. Data for studies meeting all inclusion criteria were extracted into a standardised Excel-based form by one reviewer and validated by a second reviewer. A third reviewer was consulted to resolve any discrepancies, as necessary. Risk of bias was assessed using the The National Institute for Health and Care Excellence clinical effectiveness quality assessment checklist.

Results: In total, 26 RCTs were included. For HAQ-DI, SF-36 PCS and SF-36 MCS scores, intravenous tumour necrosis factor (TNF) alpha inhibitors generally ranked higher than most other classes of therapies available to treat patients with PsA. For almost all outcomes, several interleukin (IL)-23, IL-17A, subcutaneous TNF and IL-12/23 agents offered comparable improvement, while cytotoxic T-lymphocyte-associated antigen 4, phosphodiesterase-4 and Janus kinase inhibitors often had the lowest efficacy.

Conclusions: While intravenous TNFs may provide some improvements in PROs relative to several other tsDMARDs and bDMARDs for the treatment of patients with PsA, differences between classes of therapies across outcomes were small.

Keywords: Adult dermatology; Psoriasis; RHEUMATOLOGY.

Figure 1

Evidence network for HAQ-DI. BIW, twice weekly; HAQ-DI, Health Assessment Questionnaire Disability Index; LD, loading dose; Q2W, every 2 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks.

Figure 2

League table of mean differences for change from baseline in HAQ-DI. Interventions are ordered from top-left to bottom-right in order of decreasing mean rank. For each pairwise comparison, the row treatment serves as the reference group. Pairwise comparisons from the unadjusted, random effects NMA model are shown in terms of MDs and 95% CrIs. An MD<0 favours the treatment in a given column. MDs with CrIs that do not span zero are shown with a grey background. ABA, Abatacept; ADA, adalimumab; APL, apremilast; BIW, twice weekly; CERT, certolizumab; Crl, credible interval; CTLA-4i, cytotoxic T-lymphocyte associated antigen 4 inhibitor; ETA, etanercept; GOL, golimumab; GUS, guselkumab; HAQ-DI, Health Assessment Questionnaire Disability Index; IL-17Ai, interleukin-17A inhibitor; IL-12/23i, interleukin-12/23 inhibitor; IL-23i, interleukin-23 inhibitor; INF, infliximab; IXE, ixekizumab; JAKi, Janus kinase inhibitor; LD, loading dose; MD, mean difference; NMA, network meta-analysis; PBO, placebo; PDE4i, phosphodiesterase-4 inhibitors; Q2W, every 2 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks; SEC, secukinumab; TNFi, tumour necrosis factor inhibitor; TOF, tofacitinib; UST, ustekinumab; WT, weight-based (ie, intravenous).

Figure 3

League table of mean differences for change from baseline in SF-36 MCS. Interventions are ordered from top-left to bottom-right in order of decreasing mean rank. For each pairwise comparison, the row treatment serves as the reference group. Pairwise comparisons from the unadjusted, random effects NMA model are shown in terms of MDs and 95% CrIs. An MD>0 favours the treatment in a given column. MDs with CrIs that do not span zero are shown with a grey background. ABA, Abatacept; ADA, adalimumab; BIW, twice weekly; CERT, certolizumab; Crl, credible interval; CTLA-4i, cytotoxic T-lymphocyte associated antigen 4 inhibitor; ETA, etanercept; GOL, golimumab; GUS, guselkumab; IL-17Ai, interleukin-17A inhibitor; IL-12/23i, interleukin-12/23 inhibitor; IL-23i, interleukin-23 inhibitor; INF, infliximab; IXE, ixekizumab; JAKi, Janus kinase inhibitor; MCS, Mental Component Summary; MD, mean difference; NMA, network meta-analysis; PBO, placebo; Q2W, every 2 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks; SF-36, 36-Item Short Form Survey; TNFi, tumour necrosis factor inhibitor; TOF, tofacitinib; UST, ustekinumab; WT, weight-based (ie, intravenous).

Figure 4

League table of mean differences for change from baseline in SF-36 PCS. Interventions are ordered from top-left to bottom-right in order of decreasing mean rank. For each pairwise comparison, the row treatment serves as the reference group. Pairwise comparisons from the baseline risk-adjusted, random effects NMA model are shown in terms of MDs and 95% CrIs. An MD>0 favours the treatment in a given column. MDs with CrIs that do not span unity are shown with a grey background. ABA, Abatacept; ADA, adalimumab; APL, apremilast; BIW, twice weekly; CERT, certolizumab; Crl, credible interval; CTLA-4i, cytotoxic T-lymphocyte associated antigen 4 inhibitor; ETA, etanercept; GOL, golimumab; GUS, guselkumab; IL-17Ai, interleukin-17A inhibitor; IL-12/23i, interleukin-12/23 inhibitor; IL-23i, interleukin-23 inhibitor; INF, infliximab; IXE, ixekizumab; JAKi, Janus kinase inhibitor; LD, loading dose; MD, mean difference; NMA, network meta-analysis; PBO, placebo; PCS, Physical Component Summary; PDE4i, phosphodiesterase-4 inhibitors; Q2W, every 2 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks; SEC, secukinumab; SF-36, 36-Item Short Form Survey; TNFi, tumour necrosis factor inhibitor; TOF, tofacitinib; UST, ustekinumab; WT, weight-based (ie, intravenous).