Rheumatology and Therapy

Etanercept is effective in the management of rheumatoid arthritis (RA) and can be self-administered via an auto-injector. While these devices are generally well accepted, some patients are not comfortable with the process of self-administration; this has been cited as a reason for discontinuation of biologic treatment. Alternative routes of administration (e.g., infusion) are more resource intensive. The aim of this analysis was to explore the attributes of auto-injection devices that impact patient confidence and ability to self-administer. Patients with RA (n = 168) and healthcare providers (n = 82) in Belgium, Germany, Japan, Spain, and the UK were interviewed (n = 250 overall). Mock injection procedures were carried out using an auto-injector device with the addition of a sleeve with a wider rubber grip. Importance of and performance of the device against a range attributes were captured using a Likert scale (1–7). Disease severity was captured using the Cochin hand function scale. Device attributes reported by patients to be most important were ‘use without assistance’ ‘ease of administration’, ‘ease of operation’, and ‘ease of grip’. The device with additional sleeve performed strongly against these attributes, scoring 6.9 (out of 7), 6.8, 6.8, and 6.6, respectively with no difference observed between countries. Nurses and physicians reported similar responses. Qualitatively, patients reported that stability and grip provided a sense of control and reduced anxiety. Similar overall ‘ease of operation’ was reported between patients with mild (n = 89) or moderate/severe (n = 71) disease (score 6.4 vs. 6.5, respectively). The auto-injector plus sleeve performed strongly against key attributes even in patients with moderate/severe RA and patients with reduced grip strength. The robust grip improved patient confidence and reduced injection-related anxiety. This may be beneficial in patients who are anxious about self-administration, those new to self-administration, and potentially in patients with reduced hand dexterity as a result of either advanced disease or a painful day. Etanercept is a medicine used to treat rheumatoid arthritis that is given by injection. It can be delivered by patients themselves, in their own homes, using an auto-injection device that looks like a pen. Some patients are not comfortable with the process of self-injecting. Other patients have severe arthritis in their hands that stops them from carrying out self-injection. One auto-injection device (MyClic) has been enhanced by the addition of a sleeve that fits over the top of the pen. This was shown to 168 patients with rheumatoid arthritis, who already use the MyClic ‘pen’ and 82 doctors and nurses in five countries (Belgium, Germany, Japan, Spain, and the UK). Patients, nurses, and doctors said what they believed to be the most important features of a self-injection device. Generally, patients, nurses, and doctors from the different countries had similar views. Next, the participants scored the modified auto-injection device against those features. The device plus sleeve scored highly, meaning that patients, nurses, and doctors believed it would work well for the patient population tested. Many patients said that with the added sleeve, the self-injection device was more stable and they were able to grip it better. This helped to make patients feel in control and reduced any anxiety or fear they were feeling about their self-injection. This suggests that the sleeve is a useful addition and may be particularly useful for patients who are nervous about self-injection or have difficulty gripping self-injection devices because of their arthritis.

This retrospective, observational study aimed to analyze and assess adherence, persistence, dosing, and use of concomitant medications of seven self-administered target drugs (abatacept, golimumab, secukinumab, tocilizumab, ustekinumab, apremilast, and tofacitinib) that are currently available in Canada for the treatment of inflammatory arthritis (IA). We used IQVIA’s longitudinal claims databases, which include private drug plans and public plans. Patients with IA identified using a proprietary indication algorithm who initiated treatment with any of the target drugs between January 2015 and February 2019 were selected and followed for 12 months. Golimumab and apremilast had the highest proportion of patients (~ 75%) who were bio-naïve and secukinumab had the fewest bio-naïve patients (~ 43%). The oral therapies, apremilast and tofacitinib, had the lowest percentage of adherent patients (73% and 71%) followed by abatacept (83%), while the remaining drugs had adherence around 90%. Secukinumab and tofacitinib had the highest 12-month persistence rate (63% and 61%), while abatacept and apremilast had the lowest persistence rate (52% and 47%). Oral corticosteroid (OCS) use was not significantly associated with adherence. Tocilizumab, secukinumab, and ustekinumab had the highest proportion of patients (> 20%) with dose escalation at 3–4 months from index. OCS and conventional disease-modifying antirheumatic drugs (cDMARD) use decreased in post-index period across all target drugs. This study identified substantial differences in patient baseline characteristics. Patients on injectable biologics were more likely to be adherent compared with those on oral drugs, possibly owing to longer dosing intervals. Other outcomes at 12 months appeared similar as evidenced by tapering of concomitant medications, although differences in persistence and dose escalation were noted.

Patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) may receive suboptimal care, and differences in care by race/ethnicity, sex, and insurance coverage are not well studied. This was a descriptive, retrospective cross-sectional US claims database analysis utilizing the Medicaid multi-state segment of the IBM® MarketScan® Commercial Claims and Encounters Supplemental Database and Optum Insight Clinformatics® Data Mart database for 2019. Patients aged ≥ 18 years with PsA or AS and continuous medical and pharmacy coverage were included. Outcomes evaluated were prevalence and percentage of patients receiving biologic disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic DMARDs (tsDMARDs) or visiting a rheumatologist. Outcomes were stratified by race/ethnicity, sex, and insurance coverage, with outcomes determined for commercial insurance, Medicare, and Medicaid enrollees. Differences observed in outcomes were numerical in nature. Prevalences of PsA and AS were highest for Medicare enrollees (320 and 156 per 100,000 persons [0.32 and 0.16%], respectively) and lowest for Medicaid enrollees (132 and 71 per 100,000 persons [0.13 and 0.07%], respectively). White patients had the greatest prevalence versus patients of other races/ethnicities. Females had a higher prevalence of PsA than males, while AS prevalence was generally lower for females versus males for each insurance category. The percentage of patients prescribed bDMARDs/tsDMARDs was highest for commercial insurance enrollees (PsA 63%, AS 43%) and lowest for Medicare enrollees (PsA 21%, AS 11%). The proportion of patients who saw a rheumatologist was lower for Medicaid enrollees (PsA 12%, AS 10%) than for commercial insurance or Medicare enrollees (PsA 68%, 55%; AS 67%, 42%). For commercial insurance and Medicare enrollees, the percentage of patients visiting a rheumatologist was similar by race/ethnicity but higher for females versus males. The prevalence and treatment of PsA and AS differs by race/ethnicity, insurance coverage, and sex in the USA. Efforts for improving access to care are needed to improve outcomes among all patients.

Evaluate tolerability and effectiveness of golimumab-IV versus infliximab in patients with rheumatoid arthritis (RA) in a real-world setting. AWARE, a prospective, real-world, pragmatic, observational, multicenter, phase 4 study, enrolled RA patients when initiating golimumab-IV or infliximab. Treatment decisions were made by the treating rheumatologist. The approved doses for RA are 2 mg/kg at weeks 0, 4, then Q8W for golimumab-IV and 3 mg/kg at weeks 0, 2, 6, then Q8W (dose escalation permitted) for infliximab. A prespecified formal interim analysis was conducted. The primary endpoint was the incidence of infusion reactions (any adverse event that occurred during or within 1 h of infusion) through week 52. Major secondary endpoints were mean change from baseline in CDAI at months 6 and 12 in biologic-naïve patients (non-inferiority margin in the CDAI = 6). Baseline characteristics were adjusted using propensity scores with inverse probability of treatment weights (IPTW). In the formal interim analysis (golimumab-IV, n = 479; infliximab, n = 354), the incidence of infusion reactions was significantly lower with golimumab-IV vs. infliximab (3.6 vs. 17.6%, p < 0.001, IPTW-adjusted). Among biologic-naïve patients, mean changes from baseline in CDAI at month 6 (– 9.5 golimumab-IV vs. − 10.1 infliximab) and at month 12 (− 9.4 golimumab-IV vs. − 10.1 infliximab) demonstrated non-inferiority. The proportion of patients with an infusion reaction was significantly lower with golimumab-IV vs. infliximab. Among biologic-naïve patients, mean change from baseline in CDAI at months 6 and 12 was non-inferior for golimumab-IV vs. infliximab. Compared with fixed-dose golimumab-IV, infliximab dose escalation did not provide any greater improvements in CDAI for patients with RA. ClinicalTrials.gov identifier, NCT02728934.

The objective of this report was to evaluate perceptions of psoriatic arthritis (PsA) treatment and satisfaction with healthcare professional (HCP) communication among patients with PsA in Australia, compared with overall global perceptions. Data were collected via a global and country-specific survey (The Harris Poll; November 2, 2017–March 12, 2018). Eligible patients were ≥ 18 years old, had been diagnosed with PsA > 1 year prior, had seen a rheumatologist or dermatologist within the past 12 months, and had previously received ≥ 1 conventional synthetic or biologic disease-modifying antirheumatic drug. Data reported by patients included baseline demographics, overall health, time since PsA diagnosis, PsA severity, satisfaction with current PsA medication and management, and experiences regarding communication with their HCP. Descriptive statistics were obtained. Most patients in Australia were very or somewhat satisfied with their PsA medication, and reported always or often taking their medication exactly as directed by their HCP. However, the majority still experienced symptoms, reported their overall health as poor or fair, and would change something about their PsA medication. While the majority of patients in Australia were satisfied with the communication with their HCP, most would prefer increased communication but some felt that asking too many questions would affect the quality of their care. Perceptions in Australia were similar to global perceptions. Although most patients with PsA in Australia were satisfied with their disease management and communication with their HCP, many still experienced symptoms, would change something about their PsA medication, and would prefer increased communication with their HCP. Psoriatic arthritis (PsA) can cause tender and swollen joints. If not treated properly, the joint damage can get worse, until patients struggle to cope with everyday tasks. Patients and their doctors need to communicate well to successfully manage PsA. We used an online survey to ask patients in Australia how they feel about their PsA medication and the way they communicate with their doctor. These patients were adults who had had PsA for more than 1 year, had seen a specialist doctor in the past year, and had taken one or more prescription PsA medications. A total of 152 patients in Australia completed the survey. Most patients were very or somewhat satisfied with the PsA medication they were taking, and most always or often took it exactly as their doctor told them to. However, almost all patients still had symptoms, most said their overall health was poor or fair, and most would like to change something about their medication. While most patients were satisfied with the communication with their doctor about PsA, most wished they talked more with their doctor about their PsA and treatment goals, but some felt that asking too many questions would harm their quality of care. Patients in Australia had similar answers to patients who answered the survey in other countries. Although the survey was limited by the number of patients who responded, and whether patients answered questions properly, it suggests that patients and doctors need to communicate more closely to improve PsA management.

Skin ulcers (SU) represent one of the most frequent manifestations of systemic sclerosis (SSc), occurring in almost 50% of scleroderma patients. SSc-SU are often particularly difficult to treat with conventional systemic and local therapies. In this study, a preliminary evaluation of the role and effectiveness of blue light photobiomodulation (PBM) therapy with EmoLED® in the treatment of scleroderma skin ulcers (SSc-SU) was performed. We retrospectively analyzed 12 consecutive SSc patients with a total of 15 SU on finger hands. All patients were treated with adequate systemic therapy and local treatment for SU; after a standard skin ulcer bed preparation with debridement of all lesions, EmoLED® was performed. All patients were locally treated every week during 2 months of follow-up; SU data were collected after 4 weeks (T4) and 8 weeks (T8). Eight SSc patients with comparable SU were also evaluated as controls. The application of EmoLED® in addition to debridement apparently produced faster healing of SU. Complete healing of SU was recorded in 41.6% cases during EmoLED® treatment. Significant improvements in SU area, length, and width, wound bed, and related pain were observed in EmoLED® patients from T0 to T8. Control subjects treated with standard systemic/local therapies merely showed an amelioration of SU area and width at the end of the follow-up. No procedural or post-procedural adverse events were reported. The positive clinical results and the absence of side effects suggest that EmoLED® could be a promising tool in the management of SSc-SU, with an interesting role to play in the healing process in addition to conventional systemic and local treatments.

Upadacitinib (UPA) is an oral, selective Janus kinase inhibitor that has demonstrated favorable efficacy with an acceptable safety profile across a global, phase 3 program in rheumatoid arthritis (RA). This phase 2 open-label extension investigated the efficacy and safety of UPA through 6 years of treatment. Patients from two phase 2b trials (BALANCE-1 and -2) enrolled in BALANCE-EXTEND (NCT02049138) and received open-label UPA 6 mg twice daily (BID). Dose increases to 12 mg BID were required for patients with < 20% improvement in swollen or tender joint counts at weeks 6 or 12 and permitted for those not achieving Clinical Disease Activity Index (CDAI) low disease activity (LDA; CDAI 2.8 to ≤ 10). Dose reduction to UPA 6 mg BID was permitted only for safety or tolerability reasons. After January 2017, the 6/12 mg BID doses were replaced by 15/30 mg once-daily extended-release equivalents. Efficacy and safety were monitored up to 6 years of UPA treatment; outcomes included rates of achievement of LDA or remission. Data were analyzed for patients who received the lower UPA dose throughout; titrated up to the higher UPA dose from weeks 6 or 12; or titrated to the higher UPA dose and back down. Overall, 493 patients entered BALANCE-EXTEND (‘Never titrated’, n = 306; ‘Titrated up’, n = 149; ‘Titrated up and down’, n = 38), and 223 patients (45%) completed the 6-year study. Total cumulative exposure was 1863 patient-years. Rates of LDA and remission were maintained through 6 years. Overall, 87%/70%/73% of patients in the ‘Never titrated’/‘Titrated up’/‘Titrated up and down’ groups achieved CDAI LDA at week 312, while the respective rates of Disease Activity Score 28 with C-reactive protein meeting LDA and remission criteria were 85%/69%/70% and 72%/46%/63%. Improvements in patient-reported outcomes were similar among the three groups. No new safety signals were identified. In this open-label extension of two phase 2 studies, UPA demonstrated sustained efficacy and an acceptable safety profile through 6 years of treatment in patients who completed the study. These data support a favorable long-term benefit–risk profile of UPA in patients with RA. Trial registration number: NCT02049138.

There is limited evidence on the consumption of analgesics in real-world large cohorts of patients with osteoarthritis (OA), especially in those with comorbidities. We aimed to characterize the use of pharmacological analgesic treatments, evaluate standardized comorbidity rates, and assess treatment trends. Our hypotheses were: (1) OA patients generally consume low and inconsistent pharmacological analgesic treatments; (2) analgesic treatment is often non-congruent with comorbidity-related safety concerns. The study was carried out at the second largest health maintenance organization in Israel. Members aged 18 years or above who were diagnosed with OA before December 31, 2018, were included. Information was obtained from the members' electronic medical record (EMR) including data on dispensed prescriptions, which were used to estimate analgesic consumption. A total of 180,126 OA patients were included in our analyses; analgesics were dispensed to 64.2% of the patients, with oral NSAIDs and opioids dispensed to 34.1 and 22.9% of the OA population, respectively. Analgesic use increased with time lapsed from OA diagnosis (p < 0.001), up to a median of 59 days covered (IQR, 20–175) after 21 years. Rates of most comorbidities in the OA population were higher compared to the MHS general population. Patients with comorbidities used more NSAIDs and opioids compared to those without them. Most OA patients use analgesics, usually oral NSAIDs. Analgesic use remains relatively low throughout the years, indicating that many OA patients are not being treated pharmacologically for pain on a regular basis. Despite having higher rates of several comorbidities compared to MHS general population, many OA patients are still treated with analgesics that can be associated with a worsening in comorbidity.

Post-menopausal women with osteoporosis > 70 years of age at high risk of fracture urgently require treatment for fracture prevention. Moreover, persistence with osteoporosis therapy is critical for real-world effectiveness. We estimated persistence with denosumab in older women at high fracture risk in clinical practice in Bulgaria. Eligible participants were post-menopausal women, > 70 years of age, diagnosed with osteoporosis (T-score ≤ − 2.5) and at high risk of fracture (≥ 3% for hip and ≥ 20% for major osteoporotic fracture) who received at least one denosumab injection before enrollment. Planned follow-up was 24 months. The primary endpoint was persistence to denosumab at 12, 18, and 24 months (defined as receiving all denosumab injections within 6 months ± 60 days of the previous injection). 250 women were enrolled across 12 Bulgarian endocrinology/rheumatology practices; median follow up, 736 days. Mean (SD) age was 75.8 (4.2) years; mean (SD) FRAX® was 13.1 (8.6) for hip and 26.1 (9.5) for major osteoporotic fracture; 47 (18.8%) women had prior osteoporosis therapy and 104 (41.6%) had prior fracture. Denosumab persistence was high: 98.0%, 92.4%, and 84.4% at 12, 18, and 24 months, respectively. A total of 42 (16.8%) women discontinued denosumab during follow-up, mostly for financial reasons [25/42 (59.5%)] or loss to follow-up [8/42 (19.0%)]. After 24 months of denosumab treatment, BMD T-score improvement to the range of osteopenia (− 2.5 ≤ T < − 1.5) was achieved by 42.4% at the femoral neck, 23.6% at the lumbar spine, and 49.2% at the total hip; complete recovery (T-score ≥ − 1.5) was observed in 9.0%, 26.4%, and 23.0% respectively. New fracture was reported in 5 patients (2%). Even in an elderly population, persistence with denosumab was high despite the challenge imposed by the 50% co-pay in Bulgaria. Bulgarian Drug Agency, №HИП-0009 (registered 28.06.2017); Central Ethics Commission: №КИ-41 (registered 16.05.2017)