Exploring the Effects of Ixekizumab on Pain in Patients with Ankylosing Spondylitis Based on Objective Measures of Inflammation: Post Hoc Analysis from a Large Randomized Clinical Trial.

INTRODUCTION: The objective of this analysis is to evaluate the improvement in spinal pain with ixekizumab, placebo, and adalimumab based on objective measures of inflammation response in patients with ankylosing spondylitis (AS). METHODS: The COAST-V 52-week, double-blind, placebo-controlled, randomized phase III trial examined the efficacy of ixekizumab in patients with active AS; adalimumab was used as an active reference arm. Treatment effects on reduction in pain were assessed by objective measures of controlled and persisting inflammation (defined by magnetic resonance imaging [MRI], C-reactive protein [CRP], or MRI + CRP status). Pathway analysis was used to analyze treatment effect that was not attributable to reduction in inflammation biomarkers. RESULTS: In patients with AS, when inflammation was controlled as assessed by MRI, patients treated with ixekizumab experienced a reduction in spinal pain at night (SP-N, numeric rating scale, ixekizumab mean = - 3.9, p < 0.001, adalimumab mean = - 2.6, p < 0.05) compared to placebo (mean = - 1.6) at week 16. When inflammation was controlled as assessed by MRI + CRP, ixekizumab and adalimumab had numerically greater reductions at week 16 in SP-N versus placebo. All ixekizumab groups had further improvements at week 52. When inflammation was persisting as assessed by MRI + CRP, ixekizumab-treated patients had significant reduction in SP-N (mean = - 3.7, p < 0.001) versus placebo (mean = - 1.7), improvement with adalimumab did not reach significance (mean = - 2.6, p = 0.06). In the pathway analysis at week 16, ixekizumab had a greater effect on pain outcomes compared to adalimumab. CONCLUSION: This post hoc analysis is supportive of the hypothesis that ixekizumab reduces pain in AS by additional mechanisms other than the reduction of measurable inflammation. TRIAL REGISTRATION NUMBER: NCT02696785.

Satisfaction with the Injection Experience of a New, Citrate-Free Formulation of Ixekizumab.

INTRODUCTION: A new, citrate-free ixekizumab formulation, which is bioequivalent to the original formulation, was associated with significant reduction in injection site pain. This study evaluates patient satisfaction with the first injection experience of citrate-free ixekizumab in a real-world setting. METHODS: A non-interventional, observational, web-based survey of adults (≥ 18 years) with psoriasis, psoriatic arthritis, or axial spondyloarthritis was conducted between August 2022 and March 2023. Patients enrolled in the Taltz US Customer Support Program were identified as receiving either the original ixekizumab or initiating citrate-free ixekizumab. Patients receiving original ixekizumab completed one survey at baseline to assess satisfaction with the formulation and one survey after switching to assess satisfaction, willingness to continue using and recommending citrate-free ixekizumab, and formulation preference. Participants previously exposed to ixekizumab completed one survey to assess their satisfaction and willingness to continue using and recommending citrate-free ixekizumab. Descriptive and comparative statistics are reported for patients that switched from original to citrate-free ixekizumab (n = 361); and descriptive statistics are reported for patients not previously exposed to ixekizumab (n = 90). RESULTS: A total of 451 patients were included in the analysis. Significantly more patients were satisfied with their first injection with citrate-free ixekizumab compared to original ixekizumab (83.9% vs. 71.7% respectively; p = 0.0001). Almost all patients who switched from original ixekizumab were definitely or mostly willing to continue using and recommending citrate-free ixekizumab (93.9% and 93.4%, respectively). Additionally, 94.2% of patients who switched from original to citrate-free ixekizumab preferred citrate-free ixekizumab or had no preference. Three-fourths of patients not previously exposed to ixekizumab were satisfied with their first injection with citrate-free ixekizumab and 94.5% were definitely or mostly willing to continue using citrate-free ixekizumab. CONCLUSION: The citrate-free ixekizumab formulation was preferred and well accepted by most patients who switched from the original ixekizumab formulation. Similar findings were seen for those newly initiating citrate-free ixekizumab.

Association of the clinical components in the distal interphalangeal joint synovio-entheseal complex and subsequent response to ixekizumab or adalimumab in psoriatic arthritis.

OBJECTIVES: To assess the frequency of simultaneous distal interphalangeal (DIP) joint disease and adjacent nail psoriasis (finger unit) among patients with psoriatic arthritis (PsA) and compare the efficacy of the interleukin (IL)-17A antagonist ixekizumab (IXE) and the tumour necrosis factor (TNF)-α inhibitor adalimumab (ADA). METHODS: This post hoc analysis evaluated the simultaneous occurrence of DIP joint involvement (tenderness and/or swelling) and adjacent nail psoriasis among patients with PsA from the SPIRIT-H2H (NCT03151551) trial comparing IXE to ADA. Among patients with simultaneous DIP joint involvement and adjacent nail psoriasis in ≥ 1 digit at baseline, treatment effects were assessed through week 52 for each affected finger unit; 'finger unit' defines the connected DIP joint and adjacent nail of an individual digit. RESULTS: A total of 354 patients had simultaneous DIP joint involvement and adjacent nail psoriasis in ≥ 1 finger unit at baseline. Among them, 1309 (IXE = 639, ADA = 670) finger units had baseline DIP joint tenderness and/or swelling and adjacent nail psoriasis. Proportions of affected finger units achieving complete resolution were significantly higher with IXE vs ADA as early as week 12 (38.8% vs 28.4%, p< 0.0001) and at all post-baseline assessments through week 52 (64.9% vs 57.5%, p= 0.0055). CONCLUSIONS: In this study cohort, patients with DIP joint involvement almost always had adjacent nail psoriasis. Greater resolution of DIP joint tenderness, swelling, and adjacent nail psoriasis was achieved at all timepoints over 52 weeks through targeting IL-17A with IXE than TNF-α with ADA, which is noteworthy given prior comparable musculoskeletal outcomes for both drug classes.

Evaluating the efficacy of biologics with and without methotrexate in the treatment of psoriatic arthritis: a network meta-analysis.

INTRODUCTION: An important consideration in the treatment of patients with psoriatic arthritis (PsA) is whether the addition of methotrexate (MTX) to biologics has greater efficacy than biologic monotherapy with respect to efficacy outcomes in these patients. OBJECTIVES: To conduct a network meta-analysis (NMA) comparing biologics by treatment class with and without MTX for treatment of adults with active PsA. METHODS: A systematic literature review (SLR) identified randomised, double-blinded, controlled trials, and a Bayesian NMA compared biologics with and without MTX by treatment class (tumour necrosis factor inhibitors (TNFi), interleukin-23 inhibitors (IL-23i) and IL-17i). Efficacy outcomes included American College of Rheumatology 20%, 50% and 70% (ACR20, ACR50 and ACR70) improvement response. RESULTS: The SLR initially identified 31 studies, of which 17 met feasibility criteria for the NMA by containing the 'without MTX' subgroup. For ACR20 efficacy (the most robust assessment examined), all active treatments were significantly better than placebo. No statistically significant differences were demonstrated between biologic monotherapy (for all classes examined) and biologics in combination with MTX for ACR20/50. IL-17i were comparable to IL-23i, and IL-17i were significantly better than TNFi for ACR20. Although limited by fewer trials, TNFi, IL-23i and IL-17i were not statistically different for ACR50/70. CONCLUSIONS: Concomitant use of MTX and biologics did not improve ACR efficacy outcomes versus biologic monotherapy. MTX does not appear to be necessary as a background therapy when biologics are used for the achievement of ACR20/50 responses in patients with PsA.

Effectiveness of bDMARDs in ankylosing spondylitis patients by biologic use: experience from the CorEvitas PsA/SpA Registry.

OBJECTIVE: To describe bDMARD initiators by biologic experience among ankylosing spondylitis (AS) patients and change in disease activity and patient-reported outcomes (PROs) in real-world US patients. METHODS: We included patients ≥18 years with AS based on physician diagnosis enrolled between 3/2013 and 11/2019 in the CorEvitas Psoriatic Arthritis (PSA)/Spondyloarthritis Registry (NCT02530268). Patients concurrently diagnosed with PSA were excluded. Baseline (bDMARD initiation) demographics, comorbidities, disease characteristics, treatment, and PROs were collected. Response rates and changes in disease activity and PROs between baseline and 6- and 12- month follow-up visits were calculated. RESULTS: Of the 489 AS patients in the PsA/SpA Registry, 254 AS (52.0%) patients initiated a bDMARD at enrollment or during follow-up (total initiations: AS = 313). Of the 313 AS initiations, 179 (57.2%) had a 6-month follow-up, 122 (39.0%) had a 12-month follow-up, and 94 (30.0%) had a 6- and 12-month follow-up visit. For those AS initiators with a 6-month follow-up, the mean age was 49.1 years, 44.4% were female, and 70.4%, 47.5%, 96.1%, and 46.9% had never used cDMARDs, TNFis, non-TNFis, and bDMARDs, respectively. Of these 179 AS initiators, 20.1% and 14.0% achieved ASAS20/40, respectively. Further, only 34% achieved low disease activity (ASDAS <2.1). When stratified by biologic-naivete and biologic-experience, the ASAS 20/40 achievement rates were 26.2% and 14.7%, and 21.4% and 7.4%, respectively, for this cohort. CONCLUSION: Although AS patients initiate bDMARDs, many do not achieve optimal treatment responses. Future research is needed to investigate the aspects associated with inadequate improvement and treatment response to bDMARDs.

Recapture and retreatment rates with ixekizumab after withdrawal of therapy in patients with axial spondyloarthritis: results at week 104 from a randomised placebo-controlled withdrawal study.

OBJECTIVES: To evaluate the recapture of response with open-label (OL) ixekizumab (IXE) retreatment at week 104 in patients with axial spondyloarthritis who flared after withdrawal of IXE therapy. METHODS: COAST-Y (NCT03129100) is a phase III extension study that included a double-blind, placebo-controlled, randomised withdrawal-retreatment period (RWRP). Patients who achieved remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 (inactive disease, ID) at least once at week 16 or 20 and <2.1 (low disease activity, LDA) at both visits) were randomised 2:1 at week 24 to continue IXE or withdraw to placebo. Patients who subsequently flared were switched to OL IXE every 2 or 4 weeks (Q2W or Q4W) at the next visit. The proportions of patients who recaptured ASDAS LDA and ID were summarised for those who experienced flare. RESULTS: Of the 155 patients who entered the RWRP (placebo, n=53; IXE Q4W, n=48; IXE Q2W, n=54), 138 (89%) completed week 104. Of the placebo-treated patients (n=53), 28 (53%) experienced a flare during weeks 24-104; of these, 4 (14%) recaptured ASDAS LDA before retreatment with OL IXE, and 23 (82%) recaptured ASDAS LDA and 19 (68%) met ASDAS ID after retreatment. Of the continuously treated IXE patients (n=102), 13 experienced flare; 7 of 13 (54%) recaptured ASDAS LDA before switching to OL IXE retreatment, while 5 of 13 (38%) recaptured ASDAS LDA and 4 of 13 (31%) met ID after switching. CONCLUSIONS: Ninety-six per cent of patients withdrawn to placebo recaptured at least ASDAS LDA and 71% recaptured ASDAS ID with IXE retreatment at week 104. This may provide support to patients who may require a brief interruption in therapy.

Identifying inadequate response among patients with ankylosing spondylitis and psoriatic arthritis prescribed advanced therapy in a real-world, commercially insured adult population in the USA.

OBJECTIVE: This study aimed to assess treatment patterns and frequency of inadequate response associated with advanced therapy initiation among patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in the USA. METHODS: Adult patients with AS or PsA who initiated advanced therapy were identified from the HealthCore Integrated Research Database®. Inadequate response to advanced therapies (tumour necrosis factor inhibitors [TNFi] and non-TNFi biologics) was identified using a claims-based algorithm. Factors influencing inadequate response were assessed using multivariable logistic regression. RESULTS: In total, 646 patients with AS, and 1433 patients with PsA were evaluated. Among patients with AS (mean age, 43 years; male, 58%), 93% patients initiated TNFi, and 69% of patients had inadequate response. In patients with PsA (mean age, 49 years; male, 47%), 67% initiated TNFi, and 77% had inadequate response. Low adherence was the main predictor of inadequate response in patients with AS (56%) and PsA (63%). Inadequate responders were more likely to be female (odds ratio [OR] 2.05 for AS and 1.37 for PsA). Prior exposure to TNFi was associated with 3.89- and 2.14-fold greater odds of inadequate response in both AS and PsA patients, respectively, while patients using methotrexate were less likely to have inadequate response (OR 0.48 for AS and 0.72 for PsA; all p < 0.05). CONCLUSIONS: Over 69% of patients with AS and 77% of patients with PsA had inadequate response to their index advanced therapy during 1 year after initiation. Health plan claims data appear useful to classify inadequate responders in AS and PsA. Key Points • Estimating inadequate response to advanced therapies and identifying factors associated with this outcome using claims data could improve treatment outcomes in AS and PsA. • In a sample of commercially insured US patients, over 69% of patients with AS and 77% of patients with PsA had inadequate response to their index advanced therapy during 1 year after initiation. Patient characteristics such as sex and prior therapy use were predictive of inadequate response to advanced therapies. • Health plan claims data appear useful to classify inadequate responders in AS and PsA and identify factors associated with this outcome.

Employment, Work Productivity, and Biologic Treatments in Self-Reported Axial Spondyloarthritis: a Cross-Sectional Study in a Female Predominant Population from the ArthritisPower Registry.

INTRODUCTION: The aim of this study was to characterize employment, work productivity, and biologic disease-modifying anti-rheumatic drug (bDMARD) treatment in a predominantly female population of axial spondyloarthritis (axSpA) patients in a real-world setting. METHODS: This was a cross-sectional study of axSpA participants within the ArthritisPower registry. Outcomes were assessed with surveys (Work Productivity and Activity Impairment [WPAI], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], and Patient-Reported Outcomes Measurement Information System instruments) and compared between subgroups (employed vs. not employed; taking vs. not taking a bDMARD). RESULTS: Among the 195 participants, 117 (60.0%) were employed and 78 (40.0%) were not employed entirely or partially due to axSpA. The mean age of the participants was 47.6 years and 86.7% were female. Current bDMARD use was reported by 57.4% of those surveyed (59.8% employed vs. 53.9% not employed; p = 0.408). Compared to not employed participants, employed participants had more favorable disease activity (BASDAI 6.0 vs. 7.6; p < 0.001) and overall health (self-rated health 2.5 vs. 1.8; p < 0.001). Employed participants, compared to not employed participants, were diagnosed at an earlier age (36.0 vs. 42.5 years, respectively) and experienced a shorter time between symptom onset and diagnosis (9.5 vs. 13.6 years, respectively). Employed participants reported missing on average 6.5 days of work and experienced a 52.7% impairment on work productivity due to axSpA over a 3-month period. Absenteeism and presenteeism were statistically similar between participants taking a bDMARD versus those not taking a bDMARD. CONCLUSIONS: Although bDMARD treatment rates were similar between employed and not employed participants, disease activity and overall health were better in employed than non-employed participants. Employed participants experienced substantial work productivity impairment due to axSpA.

Patient Perspectives on Biologics for Axial Spondyloarthritis in a Cross-sectional Study in a Predominantly Female Population: Treatment Satisfaction, Wear-off Between Doses, and Use of Supplemental Medication.

INTRODUCTION: There is limited information regarding treatment experience of patients with axial spondyloarthritis/ankylosing spondylitis (axSpA/AS) receiving biological disease-modifying antirheumatic drugs (bDMARDs). Here we characterize patient experiences and perspectives, including satisfaction among those currently treated with bDMARD therapy for axSpA/AS. We also assess the use of supplemental medication during perceived wear-off between doses. METHODS: Adult participants from the United States within the ArthritisPower registry with physician-diagnosed axSpA/AS were invited to complete electronic patient-reported outcome measures and an online survey about their perspectives of treatment. Analysis compared patient characteristics and treatment satisfaction by whether wear-off in axSpA/AS between bDMARD doses was reported. RESULTS: Of 128 patients currently taking a DMARD, the mean age was 46.9 (10.3) years, 82.0% were female, and 93.8% were White. A total of 78 (60.9%) perceived wear-off with their current bDMARD before the next dose, 19 (14.8%) did not experience wear-off and 31 (24.2%) were unsure about wear-off. Mean (standard deviation [SD]) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score indicated poor disease control in all patients receiving bDMARDs (6.4 [1.8]); worse for those perceiving wear-off between doses versus those who did not perceive wear-off or were unsure (6.8 [1.6] vs. 5.9 [2.0], p = 0.011). Patients experiencing wear-off reported being 'very satisfied' or 'somewhat satisfied' with their treatment less frequently than patients without wear-off (73.1 vs. 89.5%, respectively). Of patients reporting wear-off, 82.1% (n = 64) used supplemental medications during wear-off (non-steroidal anti-inflammatory drugs [68.8%, n = 44], muscle relaxants [42.2%, n = 27], and/or opioids [37.5%, n = 24]). CONCLUSIONS: In a predominantly female sample of bDMARD-treated patients with axSpA/AS and high disease activity, the majority expressed treatment satisfaction. However, most experienced wear-off between doses and relied on supplemental medications, including opioids, to manage symptoms.

Treatment Satisfaction and Decision-making from the Patient Perspective in Axial Spondyloarthritis: Real-World Data from a Descriptive Cross-sectional Survey Study from the ArthritisPower Registry.

OBJECTIVE: Aims were to 1) to characterize patient decision-making with treatment for axial spondyloarthritis (axSpA) and 2) to explore relationships among decision-making, treatment satisfaction, and biologic disease modifying antirheumatic drugs (bDMARDs). METHODS: ArthritisPower participants with physician-diagnosed axSpA were invited to complete an online survey about their treatment and their most recent physician visit. Analysis compared treatment decision by satisfaction and bDMARD status. RESULTS: Among the 274 participants, 87.2% were female, and the mean age was 50 years. Of participants, 79.5% had researched treatment before their most recent physician visit, and 56.9% discussed treatment change at their most recent physician visit. Of treatment-change discussions, 69.2% of them were related to escalation, compared with deescalation (27.6%) and/or switching (39.1%). Among those participants who discussed a change, 73.7% agreed to it because they felt that their disease was not being controlled (54.9%) or felt that it could be better controlled on new treatment (20.3%). Top symptoms prompting change were back/buttock pain (63.3%), other joint pain (55.1%), and fatigue (54.1%). Among bDMARD-treated participants (n = 128), important factors for treatment decisions were prevention of long-term axSpA consequences (92.9%) and doctor's advice (87.5%). Among 43.4% of participants reporting treatment dissatisfaction, 37% did not discuss treatment change. Current bDMARD use was more common in satisfied (61.9%) than dissatisfied participants (26.9%). CONCLUSION: In this cross-sectional study of a predominantly female axSpA population, patients frequently researched treatment options and discussed escalation with their providers. Under two-thirds of participants who were dissatisfied with treatment discussed changes at their most recent visit. Current bDMARD use was associated with higher satisfaction, and bDMARD users considered prevention of long-term consequences and doctor's advice to be very important for decision-making.

Effects of ixekizumab treatment on structural changes in the sacroiliac joint: MRI assessments at 16 weeks in patients with non-radiographic axial spondyloarthritis.

BACKGROUND: There is limited understanding regarding the inhibition of structural damage in the sacroiliac joint of patients with non-radiographic axial spondyloarthritis. This study evaluated the effect of the interleukin-17A inhibitor ixekizumab versus placebo on structural lesions in the sacroiliac joints as assessed by MRI at week 16 in patients with non-radiographic axial spondyloarthritis from the COAST-X study. METHODS: COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs. Patients were randomly allocated to placebo or double-blind ixekizumab 80 mg every 4 weeks (Q4W) or 2 weeks (Q2W), with an 80 mg or 160 mg starting dose. We report a post-hoc analysis of 266 patients with available MRI scans from baseline and week 16. MRI scans were scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint structural score (SSS) method independently by two masked readers. Treatment comparisons used analysis of covariance based on observed cases. Correlations were evaluated among changes in SPARCC SSS for erosion, fat lesions, and backfill, and between changes in SPARCC SSS and sacroiliac joint inflammation scores and clinical measures. COAST-X was registered with ClinicalTrials.gov, NCT02757352. FINDINGS: Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled to the COAST-X study. 290 (96%) of 303 participants completed the week 16 visit (95 in the ixekizumab Q4W group, 98 in the ixekizumab Q2W group, and 97 in the placebo group), and MRI scans were available for 266 patients at baseline and week 16 (85 in the ixekizumab Q4W group, 91 in the ixekizumab Q2W group, and 90 in the placebo group). Changes from baseline to week 16 in mean SPARCC SSS for erosion were -0·39 for ixekizumab Q4W (p=0·003 vs placebo), -0·40 for ixekizumab Q2W (p=0·002), and 0·16 for placebo; for fat lesions: 0·16 for ixekizumab Q4W (p=0·013), 0·10 for ixekizumab Q2W (p=0·067), and -0·04 for placebo; and for backfill: 0·21 for ixekizumab Q4W (p=0·011), 0·22 for ixekizumab Q2W (p=0·006), and -0·10 for placebo. Ankylosis did not change. Effects of ixekizumab versus placebo on structural changes were most pronounced in patients with baseline inflammation in the sacroiliac joints. Changes from baseline at week 16 in erosion, fat lesions, and backfill were correlated. INTERPRETATION: Although the clinical relevance is not yet clear, patients with non-radiographic axial spondyloarthritis receiving ixekizumab had significant reductions in erosions and increases in fat lesions and backfill in the sacroiliac joints versus placebo at week 16, suggesting an early repair process with ixekizumab treatment. FUNDING: Eli Lilly and Company.

Pain Medication and Corticosteroid Use in Ankylosing Spondylitis, Psoriatic Arthritis, and Rheumatoid Arthritis in the United States: A Retrospective Observational Study.

OBJECTIVE: We compared pain medication use in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA) versus matched control over 2 years; a subgroup analysis assessed changes in pain medication use in patients who initiated a biologic during 12 months before and after. METHODS: This was a retrospective observational cohort study using an administrative claims database. Newly diagnosed adult patients with AS, PsA, or RA identified between 1/1/2014 and 7/31/2017 were included. Demographics, baseline characteristics, and pain medication use were described using descriptive statistics. Differences in pain medication use were assessed using McNemar's/Wilcoxon signed-rank test for categorical/continuous variables. RESULTS: The study included 2180 AS, 5681 PsA, and 34,047 RA patients to assess overall pain medication use over 2 years; 188 AS, 921 PsA, and 1599 RA patients were included to assess changes in pain medication use 12 months before and after initiation of biologic. Demographics and baseline characteristics were balanced. In the overall cohort, 74.6% AS, 75.0% PsA, and 83.0% RA patients used any pain medication at baseline versus matched control; pain medications use 2 years after diagnosis date was reported in 73.5% AS, 74.1% PsA, and 81.3% RA patients. Among AS, PsA, and RA patients, use of prescribed NSAIDs (AS: 68.1 vs. 51.1%; PsA: 51.1 vs. 42.5%; RA: 61.1 vs. 41.5%; P < 0.05), glucocorticoids (AS: 56.4 vs. 41.5%; PsA: 57.4 vs. 46.9%; RA: 88.2 vs. 75.3%; P < 0.05), and opioids (AS: 42.6 vs. 36.2% [non-significant]; PsA: 38.1 vs. 33.8%; RA: 52.0 vs. 40.4%; P < 0.05) significantly decreased 12 months after biologic initiation versus prior. CONCLUSIONS: Use of NSAIDs, glucocorticoids, and opioids are common among patients with AS, PsA, or RA, although the reported use of these co-medications after biologic initiation significantly decreases in the first year of treatment.

Evaluation of Changes in Skin and Joint Outcomes and Associated Treatment Changes in Psoriatic Arthritis (PsA): Experience From the Corrona PsA/SpA Registry.

OBJECTIVE: To characterize skin severity and joint activity outcomes and associated treatment changes in patients with psoriatic arthritis (PsA) through 12 months of follow-up after enrollment in the Corrona Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry. METHODS: Patients ≥ 18 years of age with a diagnosis of PsA and a history of psoriasis between March 21, 2013, and September 30, 2016, were enrolled (n = 647). Demographics, clinical features, and treatment characteristics were collected and stratified by skin severity and joint activity. Change in joint and skin from enrollment to the 12-month visit was classified by change in category of Clinical Disease Activity Index (CDAI) or body surface area (BSA). Tests of association evaluated the relationship between changes in therapy and changes in skin severity and joint activity. RESULTS: Patients with improvement in both joint activity and skin severity saw the largest median reduction in both CDAI and BSA, while those who worsened in both had the greatest median increase in both CDAI and BSA. The majority of PsA patients (> 50%) had no change in skin severity regardless if they had reduced therapy (50%), no therapy changes (54%), or increased therapy (56%; P = 0.5875). However, there was a significant association between changes in therapy and changes in joint activity (P < 0.001). Patients who increased therapy were more likely to have improvement in joint activity (32%) compared to patients who reduced therapy (22%) or had no therapy changes (11%). CONCLUSION: The clinical implication for our findings suggests the assessment and incorporation of both skin and joint components may be advisable.

Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials.

OBJECTIVES: The aim of this integrated analysis is to evaluate the long-term safety and tolerability of ixekizumab in adults with psoriasis, PsA and axial SpA. METHODS: Integrated safety data from 21 clinical trials are presented by indication in patients who received at least one dose of ixekizumab. Adverse events (AEs) and treatment-emergent adverse events (TEAEs) adjusted incidence rates (IRs) per 100 patient-years (PY) up to 5 years' exposure are reported. RESULTS: A total of 8228 patients with an ixekizumab exposure of 20 895.9 PY were included in this analysis. The most common TEAEs were nasopharyngitis, upper respiratory tract infection and injection-site reactions. Across populations, IRs were low for AEs leading to discontinuation (IRs ≤5.1 per 100 PY), serious AEs (IRs ≤6.0 per 100 PY) and death (IRs ≤0.3 per 100 PY). The most reported TEAEs of special interest were infections (IRs ≤35.8 per 100 PY). Patients rarely reported malignancies (IR ≤0.8), IBD including ulcerative colitis and Crohn's disease (IR ≤0.8) and major adverse cardiovascular events (IR ≤0.5). TEAEs were most commonly reported the first 2 years of exposure with ixekizumab and IR decreased over the years (infections, injection-site reactions and depression) or remained constant over the entire treatment period (serious infections, major adverse cardiovascular events, malignancies and IBD). CONCLUSION: This long-term analysis on the safety of ixekizumab was consistent with previously published reports and did not show any new safety signals. The safety profile and tolerability reported in this integrated analysis remained consistent with the known safety profile for ixekizumab.

Efficacy and Safety of Long-Term Baricitinib With and Without Methotrexate for the Treatment of Rheumatoid Arthritis: Experience With Baricitinib Monotherapy Continuation or After Switching From Methotrexate Monotherapy or Baricitinib Plus Methotrexate.

OBJECTIVE: To evaluate the long-term efficacy and safety of maintaining baricitinib monotherapy in patients with active rheumatoid arthritis (RA) originally treated with baricitinib monotherapy or switched from methotrexate (MTX) or the combination of baricitinib plus MTX to baricitinib monotherapy. METHODS: This is a post hoc analysis of patients from the RA-BEGIN study who entered a long-term extension, RA-BEYOND, and were assessed for up to 24 weeks. In RA-BEGIN, MTX-naive patients with early active RA were randomized to MTX monotherapy, baricitinib 4 mg monotherapy, or baricitinib 4 mg plus MTX. At week 52, all patients entering RA-BEYOND received baricitinib 4 mg monotherapy. MTX could be prescribed during RA-BEYOND at the investigator's discretion. RESULTS: Patients in RA-BEYOND who were not rescued in RA-BEGIN (n = 423) were evaluated. Of these, 47% continued baricitinib monotherapy and 53% added MTX, with similar proportions from the 3 original arms. Patients with lower disease activity at the RA-BEYOND baseline generally continued to do well with baricitinib monotherapy as assessed by the Simplified Disease Activity Index, the Clinical Disease Activity Index, and the Health Assessment Questionnaire disability index scores. Patients prescribed MTX had higher disease activity at the RA-BEYOND baseline and had improved disease activity after the addition of MTX. Safety outcomes were similar across treatment groups. CONCLUSION: Many patients responded well to continued baricitinib monotherapy or to switching to baricitinib monotherapy from MTX monotherapy or baricitinib plus MTX, showing sustained or improved disease control. The groups of patients who had less disease control on their original therapies showed sustained or improved disease control with the addition of MTX to baricitinib.

Understanding the association between skin involvement and joint activity in patients with psoriatic arthritis: experience from the Corrona Registry.

Objective: To compare the characteristics of patients with psoriatic arthritis among patient groups stratified by degree of skin and joint involvement, and to evaluate the relationship between skin severity and joint activity. Methods: Body surface area (BSA) and Clinical Disease Activity Index (CDAI) at enrolment were analysed. Patient characteristics were stratified by skin severity and joint activity. Baseline patient characteristics, clinical and disease characteristics and patient-reported outcomes were compared. The strength of the relationship of skin severity and joint activity was evaluated using methods for categorical variables (χ2 test, Cramer's V) and continuous variables (linear regression). Results: 1542 adult patients in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry enrolled between 21 May 2013 and 20 September 2016 were analysed. Most patients in the BSA >3%/CDAI moderate/high subgroup had worse clinical and patient-reported outcomes. A significant (p<0.001) modest association (Cramer's V=0.1639) between skin severity and joint activity was observed among all patients at enrolment. Patients with higher skin severity were two times more likely to have higher joint involvement (OR 2.27, 95% CI 1.71 to 3.01). A significant linear relationship between CDAI and BSA was observed. Effect modification showed this linear relationship was modified by age, gender, insurance, work status, current therapy, Health Assessment Questionnaire, Nail visual analogue scale, minimal disease activity, dactylitis count, patient-reported pain and fatigue. Conclusion: Skin severity is modestly correlated with joint activity, and patients with higher skin severity are two times more likely to have increased joint involvement. Clinicians need to address both skin severity and joint activity in treatment decisions.

Management of asymptomatic coccidioidomycosis in patients with rheumatic diseases.

Coccidioidomycosis is an endemic fungal infection common in the southwestern United States. Some rheumatology clinics periodically screen patients with coccidioidal serology, resulting in the identification of patients who are serologically positive but without clinical symptoms. The management of such patients is unclear. A retrospective study was conducted between 2007 and 2015 at two arthritis centers in Tucson, Arizona. The asymptomatic patients were identified who were receiving disease-modifying antirheumatic agents and had a positive coccidioidal serology. Serological testing including IgM and IgG was performed by enzyme immunoassay (EIA), immunodiffusion (IDTP and IDCF), or complement fixation. Out of 71 patients who were identified with positive coccidioidal serologies, 19 were asymptomatic. 18/19 patients continued antirheumatic therapy, 13 without interruption. 13/19 patients received no antifungal treatment, including 10 who remained on antirheumatic treatment. The other six were started on fluconazole, ranging from 8 to 73 months (median 30.5 months). After a median follow-up of 43 months, no patient developed clinically active coccidioidomycosis. Overall, 14 had only a positive EIA serological test. These results suggest that continued antirheumatic therapy is safe in asymptomatic patients with positive coccidioidal serological tests and that routine implementation of antifungal treatment may not always be warranted. The findings also raise concern regarding the utility of routine serological testing of asymptomatic patients residing in the coccidioidal endemic area, mainly using the EIA test.

Executive Summary: 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.

2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.