Long-term safety of Ixekizumab in adults with psoriasis, psoriatic arthritis, or axial spondyloarthritis: a post-hoc analysis of final safety data from 25 randomized clinical trials.

BACKGROUND: We report long-term, end-of-study program safety outcomes from 25 randomized clinical trials (RCTs) in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) [including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA)] who received ≥ 1 dose of Ixekizumab (IXE) over 5 years (PsO) or up to 3 years (PsA, axSpA). METHODS: This integrated safety analysis consists of data from patients who received any dose of IXE, across 25 RCTs (17 PsO, 4 PsA, 4 axSpA). Rates of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and selected adverse events (AEs) of interest were analyzed for all pooled studies by years of therapy and overall, through March 2022. Results were reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) overall and at successive year intervals. RESULTS: Six thousand eight hundred ninety two adult patients with PsO, 1401 with PsA, and 932 with axSpA (including AS and nr-axSpA), with a cumulative IXE exposure of 22,371.1 PY were included. The most commonly reported TEAE across indications was nasopharyngitis (IRs per 100 PY: 8.8 (PsO), 9.0 (PsA), 8.4 (axSpA)). SAEs were reported by 969 patients with PsO (IR 5.4), 134 patients with PsA (IR 6.0), and 101 patients with axSpA (IR 4.8). Forty-five deaths were reported (PsO, n = 36, IR 0.2; PsA, n = 6, IR 0.3; axSpA, n = 3, IR 0.1). TEAEs did not increase during IXE exposure: IRs per 100 PY, PsO: 88.9 to 63.2 (year 0-1 to 4-5), PsA: 87 to 67.3 (year 0-1 to 2-3), axSpA: 82.1 to 55.4 (year 0-1 to > = 2). IRs per 100 PY of discontinuation from IXE due to AE were 2.9 (PsO), 5.1 (PsA), and 3.1 (axSpA). IRs per 100 PY of injection site reactions were 5.9 (PsO), 11.6 (PsA) and 7.4 (axSpA); Candida: 1.9 (PsO), 2.0 (PsA), and 1.2 (axSpA); depression, major adverse cerebro-cardiovascular events and malignancies: ≤ 1.6 across all indications. Adjudicated IRs per 100 PY of inflammatory bowel disease were ≤ 0.8 across indications (0.1 [PsO]; 0.1 [PsA]; 0.8 [axSpA]). CONCLUSIONS: In this integrated safety analysis, consisting of over 22,000 PY of exposure, the long-term safety profile of IXE was found to be consistent with previous, earlier reports, with no new safety signals identified. TRIAL REGISTRATION: NCT registration numbers for RCTs included in this integrated analysis can be found in Additional File 1.

Network meta-analyses comparing the efficacy of biologic treatments for achieving complete resolution of nail psoriasis at 24-28 and 48-52 weeks.

BACKGROUND: Available network meta-analyses (NMAs) comparing the efficacy of biologics in nail psoriasis (NP) have not included recently approved biologics such as bimekizumab nor have they provided comparisons up to 1 year. OBJECTIVE: We conducted two NMAs that update and extend results from a previous NMA comparing biologics for achieving complete resolution of NP. METHODS: Bayesian NMAs were performed using a generalized linear model with a logit link to model the binary outcome of nail clearance at weeks 24-28 and 48-52. RESULTS: For the NMA at weeks 24-28, which included seven biologics and placebo, the absolute probability of achieving complete resolution of NP was highest for ixekizumab (46.4%; 95% credibility interval [CrI] 35.2-58.0), followed by brodalumab (37.1%; 95% CrI 17.1-62.2) and bimekizumab (30.3%; 95% CrI 12.7-53.9). For the NMA at weeks 48-52, which included six biologics, the absolute probability was highest for ixekizumab (77.2%; 95% CrI 51.1-93.4), followed by adalimumab (75.6%; 95% CrI 61.5-87.3) and brodalumab (71.9%; 95% CrI 38.4-93.2). CONCLUSION: Among biologics included in these two NMAs, ixekizumab has the highest absolute probability of achieving complete resolution of NP. Results may help to inform treatment decisions for patients with NP.

Network meta-analysis comparing the efficacy of biologic treatments for achieving complete resolution of nail psoriasis.

BACKGROUND: Nail psoriasis (NP) is common and of high importance in patients with psoriasis. Complete resolution of NP at week 24‒26 is an unambiguous nail outcome accessible for indirect treatment comparison of biologics. OBJECTIVE: To evaluate the comparative efficacy of approved biologics in achieving complete resolution of NP at week 24‒26. METHODS: A network meta-analysis (NMA) was conducted to indirectly compare the efficacy of six biologics in achieving complete resolution of NP at week 24‒26 in patients with moderate-to-severe psoriasis and concomitant NP. Complete resolution of NP was defined as a score of zero on the Nail Psoriasis Severity Index (NAPSI), modified NAPSI (mNAPSI) or Physician's Global Assessment of Fingernails (PGA-F). RESULTS: The probability of achieving complete resolution of NP was highest for ixekizumab (46.5%; 95% credibility interval [CrI] 35.1‒58.0; Surface Under the Cumulative RAnking curve [SUCRA] 97%), followed by brodalumab (37.0%; 17.0‒61.0; 79%), adalimumab (28.3%; 24.4‒32.4; 62%), guselkumab (27.7%; 21.1‒35.1; 58%), ustekinumab (20.8%; 10.2‒35.2; 37%), and infliximab (0.8%; 0.0‒8.9; 17%). CONCLUSION: In patients with moderate-to-severe psoriasis and concomitant NP, ixekizumab has the greatest likelihood among approved biologics of achieving complete resolution of NP at week 24‒26. Findings should be interpreted carefully because of inherent study limitations.

Call for action: how to improve use of patient-reported outcomes to guide clinical decision making in rheumatoid arthritis.

Current guidelines for the management of rheumatoid arthritis (RA) recommend early treatment and a treat-to-target goal of remission or low disease activity. Over the past decade, this approach has been extremely successful in reducing disease activity and joint damage in patients with RA. At the same time, however, overall patient perception of well-being appears to have decreased with respect to outcome measures considered important by patients themselves, such as pain, fatigue, physical function and quality of life. The timely and effective use of patient-reported outcomes (PROs) could encourage physicians to focus more on the impact of RA on patients and how patients are feeling. This in turn would facilitate shared decision making between patients and physicians, ultimately leading to a more patient-centered approach and improved patient care. Indeed, PROs provide information about individual patients that complements information provided by physical assessment and composite scores, and can also be used to guide patient care, such as determining whether a clinic visit is needed or whether treatment modifications are necessary. This is particularly important for patients who do not achieve the aspirational target of remission or low disease activity with pharmacological treatment. A number of validated PRO questionnaires are available, but how and which PROs should be incorporated into rheumatology clinical practice as part of the decision-making process is still controversial. Combining PROs with technology, such as computer adaptive tests, electronic PRO systems, web-based platforms and patient dashboards, could further aid PRO integration into daily rheumatology clinical practice.