Outcomes of Patients With Acute Vogt–koyanagi–harada Disease Treated With Intravenous Corticosteroid Pulse Followed by the Slow Tapering of Oral Corticosteroid Therapy

Purpose We investigated the treatment outcomes of patients with acute Vogt–Koyanagi–Harada (VKH) disease and assessed the differences between patients with no inflammation worsening and those with persistent or worsening inflammation. Potential factors responsible for eyes with low visual outcomes were also investigated.Methods We retrospectively reviewed the clinical records of patients with acute VKH disease who first visited us between 2009 and 2018 and were followed up for >300 days. Clinical characteristics, treatments, and posttreatment conditions were assessed. Patients were classified into no inflammation worsening (acute–resolved [AR]) and inflammation worsening (chronic–recurrent [CR]) groups based on conditions after 6 months from disease onset.Results This study assessed 62 eyes from 31 patients (mean age: 52.8 years). One patient was treated with topical treatment alone and showed poor visual outcomes. In total, 30 patients were treated with methylprednisolone pulse followed by the slow tapering of oral prednisolone; 73% of them developed AR and 27% CR. Although the total prednisolone dose was higher in patients with CR disease, no significant difference was noted in the final best-corrected visual acuity (BCVA). Among the patients receiving systemic steroid, five eyes had a final BCVA of ≤0.5 due to anisometropic amblyopia, diabetic maculopathy, pre-existing macular hole, epiretinal membrane, and ellipsoid zone loss. Conclusions Patients with acute VKH disease treated with corticosteroid pulse followed by the slow tapering of prednisolone appear to demonstrate good visual outcomes, including patients with CR; most eyes with low visual outcomes have pre-existing conditions that explain low vision.

PolyMyalgia Rheumatica Treatment With Methotrexate in Optimal Dose in an Early Disease Phase (PMR MODE): Study Protocol for a Multicenter Double-blind Placebo Controlled Trial.

BackgroundPolymyalgia rheumatica (PMR) is an inflammatory rheumatic disease affecting people older than 50, resulting in pain and stiffness of the neck, shoulder-, and pelvic girdle. To date, glucocorticoids (GC) remain the cornerstone of treatment, but these have several drawbacks. Firstly, a large proportion of patients do not achieve GC-free remission within either the first (over 70%) or second year of treatment (over 50%). Secondly, GC-related adverse events (AE) occur in up to 65% of patients and can be severe.The current EULAR/ACR guidelines for PMR recommend early introduction of methotrexate (MTX) as a GC sparing agent in patients at risk for worse prognosis. However, earlier trials of low to medium quality only studied MTX dosages of 7.5–10 mg/week with no to modest effect. These doses may be suboptimal as MTX is recommended in higher doses (25 mg/week) for other inflammatory rheumatic diseases. The exact role, timing and dose of MTX in PMR remains unclear and therefore our objective is to study the efficacy of MTX 25 mg/week in recently diagnosed PMR patients. MethodsWe set up a double blind, randomized, placebo-controlled superiority trial (PMR MODE) to assess the efficacy of MTX 25 mg/week versus placebo in a 1:1 ratio in 100 recently diagnosed PMR patients according to the 2012 EULAR/ACR criteria. All patients will receive prednisolone 15mg/day, tapered to 0 mg over the course of 24 weeks. In case of primary non-response or disease relapse prednisolone dose will be temporarily increased. Assessments will take place at baseline, 4, 12, 24, 32, and 52 weeks. The primary outcome is the difference in proportion of patients in GC-free remission at week 52. DiscussionNo relapsing PMR patients were chosen, since the the possible benefits of MTX may not outweigh the risks at low doses and effect modification may occur. Accelerated tapering was chosen in order to more easily identify a GC-sparing effect if one exist. A composite endpoint of GC-free remission was chosen as a clinically relevant endpoint for both patients and rheumatologist and may reduce second order (treatment) effects. Trial registrationDutch trial registration, NL8366 Registered on 2020-02-10

A Case of Localized Prostate Cancer Associated with Polymyalgia Rheumatica with Marked Symptomatic Improvement after Robot-Assisted Radical Prostatectomy

A 73-year-old man visited our hospital with chief complaints of fever of unknown origin and bilateral shoulder and hip joint pain. He was initially diagnosed with polymyalgia rheumatica (PMR). Although the patient was treated with prednisolone 15 mg/day, his PMR-related symptoms did not improve. Further examination was performed as the patient was suspected of having paraneoplastic syndrome. Assessment results showed prostate cancer without metastases. After undergoing robot-assisted radical prostatectomy, the patient’s PMR-related symptoms dramatically improved. Hence, the prednisolone dose was decreased to 4 mg/day. PCa may have triggered the development of PMR through the activation of immune-mediated systemic inflammatory responses.

The fast-track outpatient clinic significantly decreases hospitalisation rates among polymyalgia rheumatica patients

Objectives This study aimed to investigate the hospitalisation rates and the reasons for hospitalisation in patients with polymyalgia rheumatica (PMR). Furthermore, it aimed to clarify the impact of a newly established Fast Track Clinic (FTC) approach on hospitalisation rates in connection with PMR diagnosis. Methods Patients diagnosed with PMR at South-West Jutland Hospital, Denmark, between 2013 and 2018 were included retrospectively. Only patients fulfilling the 2012 EULAR/ACR classification criteria were included in our cohort. An FTC for patients suspected of having PMR was established in the rheumatologic department of South-West Jutland Hospital in January 2018. Results Over 6 years (2013 to 2017), 254 patients were diagnosed with PMR, 56 of them while hospitalised. Hospitalised patients were more likely to have a higher initial CRP mean ± standard deviation (SD) 99.53 ± 59.36 vs 45.82 ± 36.96 mg/lt (p < 0.0001) and a shorter duration of symptoms (p = 0.0018). After implementing the FTC, a significant decrease in hospitalisation rates (from 20.4% to 3,5%) and inpatient days of care (mean ± SD 4.15 ± 3.1 vs 1 ± 0) were observed. No differences between the two groups were observed regarding clinical symptoms, laboratory values and initial prednisolone dose. Conclusion A substantial number of patients are hospitalised in connection with the PMR diagnosis. The FTC approach can decrease the hospitalisation rates significantly among these patients. Trial registration Retrospectively registered.

A Case of Systemic Lupus Erythematosus with Cutaneous Leukocytoclastic Vasculitis Mimicking Bullous SLE

Rarely, patients with systemic lupus erythematosus (SLE) develop bullous eruptions, a disease called bullous SLE in a narrow sense that has autoantibodies against type VII collagen. We describe an unusual case in which a patient with SLE developed extensive bullae on her lower extremities. Histologically, the bullous lesions were suggestive of leukocytoclastic vasculitis with deposition of C3 within blood vessel walls. Immunoblot analyses and enzyme-linked immunosorbent assays were negative for anti-type VII collagen antibodies. We initially considered bullous SLE, but eventually made a diagnosis of secondary vasculitis in SLE. The oral prednisolone dose was increased, and the vesiculobullous lesions resolved. The clinical presentations of cutaneous vasculitis in SLE include palpable purpura, petechiae, papulonodular lesions, and livedo reticularis. Bullous lesions seem to be uncommon. Physicians need to be aware that extensive bullae can occur as a result of secondary vasculitis in SLE, even if the patient does not exhibit high disease activity.

Glucocorticoid dosing and relapses in giant cell arteritis—a single center cohort study

Objective To investigate the relationship between real life glucocorticoid (GC) dosing and relapse rates in patients with new onset giant cell arteritis (GCA) in a single center. Methods Complete clinical data taken from the inpatient and outpatient records of consecutive GCA patients followed beyond stopping GC were retrospectively analyzed for GC doses, other immunomodulatory agents and relapses. Results We included 54 patients with GCA confirmed by biopsy or imaging and followed over their complete GC course. In the 25% dose percentile, patients who needed no pulse therapy at onset reached a dose of 15 mg prednisolone or lower at day 40, of 7.5 mg prednisolone or lower on day 169 (after 24 weeks), and were off prednisolone on day 496 (70 weeks). They were below BSR-recommended doses between week 4 and week 12 and above these after week 14. The cumulative prednisolone dose reached in this 25% quartile was 3.74 g. Of the 54 patients, 24 (44%) relapsed, only 4 of whom had stopped GC clearly (17–58 weeks) earlier than the 25% dose quartile and one was distinctly (&gt;10%) below the 25% GC percentile. Methotrexate treatment was not significantly associated with fewer relapses (p= 0.178). Conclusion Despite a long-term GC regimen with slow rates of reduction in the low dose range and high cumulative prednisolone doses, 44% of the patients relapsed. Only five (21%) of these relapses may have been prevented by adhering to the recommended GC regimen.

Adalimumab in patients with vision-threatening uveitis: real-world clinical experience

ObjectivesBiologics are rapidly emerging as an effective vision saving addition to systemic uveitis therapy. The aim of this multicentre retrospective study is to review the outcomes of a large group of patients treated with adalimumab.MethodsA retrospective chart review of patients with refractory non-infectious, active uveitis treated with adalimumab was conducted. The main outcome measures were ability to reduce prednisolone dose, ability to control uveitis, final visual acuity and time to treatment failure.ResultsForty-six patients with uveitis, treated with adalimumab were included in the study. The most common anatomical uveitis phenotype was panuveitis (n=17, 37.0%). The most common diagnosis was idiopathic uveitis (n=19, 41.3%). At their latest review (mean: 4.46 years; median 4.40 years), 35 (76.1%) patients were able to discontinue corticosteroids, 11 (23.9%) patients were able to taper to <7.5 mg/day and only 1 (2.2%) patient required 10 mg of prednisone. The mean visual acuity at the latest follow-up of the worse eye was logarithm of the minimum angle of resolution (logMAR) 0.42 (SD 0.72), while the mean visual acuity of the better eye was logMAR 0.19 (SD 0.34). Of the 89 eyes, 21 (23.6%) eyes improved by at least 2 lines, 5 eyes (5.6%) deteriorated by ≥2 lines while vision was unchanged in the remaining 63 (70.8%) eyes. The time to recurrence was 1 in 12.47 person-years for adalimumab, with a 17.4% (8 patient) relapse rate. There were no serious adverse events.ConclusionsThis study highlights the efficacy of adalimumab in patients with vision-threatening non-infectious uveitis, preserving vision and allowing reduction of corticosteroid dose.

Zytux in Refractory Myasthenia Gravis: A Multicenter, Open-Labeled, Clinical Trial Study of Effectiveness and Safety of a Rituximab Biosimilar

Objectives: Myasthenia gravis (MG) is an immune-mediated neuromuscular disorder responsive to immunomodulatory treatments. 10–20% of MGs are not responsive to conventional first-line therapies. Here, we sought to investigate the efficacy and safety of rituximab therapy in the treatment of patients with refractory MG.Methods: In a 48-week, multicenter, open-labeled, prospective cohort setting, 34 participants with refractory MG were assigned to receive infusions of Zytux, which is a rituximab biosimilar, according to a validated protocol. Clinical, functional, and quality of life (QoL) measurements were recorded at baseline, and seven further visits using the Myasthenia Gravis Foundation of America (MGFA), Myasthenia Gravis Composite (MGC), Myasthenia Gravis Activities of Daily Living profile (MG-ADL), and Myasthenia Gravis Quality of Life (MGQoL-15) scales. Besides, the post-infusion side effects were systematically assessed throughout the study.Results: The correlation analysis performed by generalized estimating equations analysis represented a significant reduction of MGC, MG-ADL, and MGQoL-15 scores across the trial period. The subgroup analysis based on the patients' clinical status indicated a significant effect for the interaction between time and MGFA subtypes on MG-ADL score, MGC score, and pyridostigmine prednisolone dose, reflecting that the worse clinical condition was associated with a better response to rituximab. Finally, no serious adverse event was documented.Conclusions: Rituximab therapy could improve clinical, functional, and QoL in patients with refractory MG in a safe setting. Further investigations with larger sample size and a more extended follow-up period are warranted to confirm this finding.Clinical Trial Registration: The study was registered by the Iranian Registry of Clinical Trials (IRCT) (Code No: IRCT20150303021315N18).

Association of initial prednisolone dose with remission, relapse, and infectious complications in adult-onset minimal change disease

Background A dose of 0.5–1 mg/kg/day of prednisolone (PSL) is administered for the initial treatment of minimal change disease (MCD). However, little is known about the optimal PSL dose for the initial treatment of MCD. Methods We conducted a retrospective multicenter cohort study of treatment-naive adult patients with MCD diagnosed by renal biopsy from 1981 to 2015 in whom PSL monotherapy was performed as the initial treatment. The exposure of interest was an initial median PSL dose of < 0.63 mg/kg/day (Group L) compared to ≥ 0.63 mg/kg/day (Group H). Cumulative remission and relapse after remission were compared between these groups using Cox regression adjusted for baseline characteristics. Results Ninety-one patients met the inclusion criteria. During a median follow-up of 2.98 years, 87 (95.6%) patients achieved complete remission, and 47.1% relapsed after remission. There was no significant difference in the remission rate between the groups at 4 weeks of follow-up (66.7 vs. 82.6%). The median time to remission in Group L was comparable to that in Group H (17.0 vs. 14.0 days). A multivariable Cox hazard model revealed that the initial PSL dose was not a significant predictor of remission. The cumulative steroid doses at 6 months, 1 year, and 2 years after treatment initiation were significantly lower in Group L than in Group H. Conclusion The initial PSL dose was not associated with time to remission, remission rate, time to relapse, or relapse rate. Therefore, a low initial steroid dose may be sufficient to achieve remission.

A randomised controlled unblinded multicentre non-inferiority trial with activated vitamin D and prednisolone treatment in patients with minimal change nephropathy (ADAPTinMCN)

Background Minimal change nephropathy (MCN) is a common cause of nephrotic syndrome in both adults and children. International guidelines recommend treatment with prednisolone 1 mg/kg/day to adults. This dose is derived from an empirically established dose in children, although children generally attain remission faster and relapse more rapidly than adults. Prednisolone is associated with multiple and serious adverse events. Activated vitamin D has been shown to reduce albuminuria in other glomerular renal diseases with a minimum of adverse events. This study tests the hypothesis that a new treatment regimen in MCN combining reduced dose prednisolone and active vitamin D is as efficient in inducing remission and has fewer and less severe adverse events than standard prednisolone. Furthermore, we aim to establish models allowing for more personalized medicine based on assessment of the individual’s prednisolone metabolism. Methods A randomised controlled multicentre non-inferior unblinded trial including 96 adult, incident patients with biopsy-proven MCN, albuminuria > 3 g/day, and an estimated glomerular filtration rate (eGFR) > 30 ml/min from renal departments in Denmark. Patients are randomised to standard prednisolone (1 mg/kg/day) or reduced prednisolone (0.5 mg/kg/day) and alfacalcidol (0.5 μg/day). The primary outcome is the rate of remissions after 16 weeks and the time from diagnosis to remission. The study will include a saliva test to characterise prednisolone pharmacokinetics and compare them to genetic variations in specific liver enzymes responsible for prednisolone metabolism. Discussion Reducing the prednisolone dose is expected to reduce the number of severe adverse events. This study will examine if reduced prednisolone dose with active vitamin D but without additional immunosuppression is feasible in the treatment of MCN and will reduce the number of adverse events. The findings can potentially change current guidelines for treatment of MCN in adults. Additional outcomes on inter-individual pharmacokinetic and metabolic variations may allow for a more personalised treatment strategy. Trial registration EudraCT 2017-001206-16, ClinicalTrials.gov NCT03210688. Registered on June 3, 2017.