Corticosteroid Tapering Research Articles

Phase III trial results with blisibimod, a selective inhibitor of B-cell activating factor, in subjects with systemic lupus erythematosus (SLE): results from a randomised, double-blind, placebo-controlled trial

BackgroundTargeted inhibitors of B-cell activating factor (BAFF) have been evaluated in phase III trials in over 4000 patients with systemic lupus erythematosus (SLE). Post hoc analyses of these studies identify...

Adrenocorticotropic hormone analogue as novel treatment regimen in ocular cicatricial pemphigoid

PurposeTo report the clinical outcome of a patient with ocular cicatricial pemphigoid, treated with adrenocorticotropic hormone gel. ObservationsA 75-year-old female with a biopsy proven ocular cicatricial pemphigoid (OCP) presented with bilateral conjunctival inflammation, fornix shortening, subepithelial fibrosis and corneal scarring. The patient was previously treated with topical steroids, topical cyclosporine and lubricating drops, and had undergone several amniotic membrane transplants due to recurrent corneal erosions. Once OCP diagnosis was established, the patient was started on oral corticosteroids (60 mg daily). In order to wean the patient off from systemic steroids, other immunomodulatory agents had been tried, including mycophenolate mofetil (1000 mg twice daily) and methotrexate (up to 25 mg weekly). However, none of these agents adequately controlled the ocular surface inflammation, and the patient experienced bilateral progressive cicatrization and corneal decompensation, as well as the development of side effects from the systemic corticosteroids, methotrexate and mycophenolate mofetil therapies. Treatment with twice weekly subcutaneous adrenocorticotropic hormone (ACTH) gel was initiated, along with tapering of systemic corticosteroids. During the 19 months treatment period, the patient demonstrated significant improvement in the ocular surface inflammation, visual acuity was stable and no significant adverse effects were observed. Systemic corticosteroids dosage was successfully reduced from 10 mg/day to none at last follow up. Conclusions and importanceACTH gel has shown to be an effective and safe treatment option for chronic, refractory and progressive ocular inflammatory disease. To the best of our knowledge, this is the first case report of a patient with OCP, treated successfully with ACTH gel. This case report may encourage ophthalmologists to employ ACTH gel in the management of OCP.

Ustekinumab IV 6 mg/kg Loading Dose Re-induction Improves Clinical and Endoscopic Response in Crohnʼs Disease: A Case Series

CASE: Ustekinumab, a monoclonal antibody to the p40 subunit shared by interleukins-12,23, is approved for treatment of patients with moderate to severe Crohn's disease(CD) with a weight-based intravenous ustekinumab induction followed by subcutaneous maintenance therapy (Feagan et al, 2016). TNF inhibitors are associated with clinical and endoscopic response. Among anti-TNF experienced patients receiving induction at Week 6, higher serum drug concentrations are associated with clinical response, suggesting that there may be a therapeutic benefit to optimizing ustekinumab drug concentrations to augment clinical response (Sandborn et al, 2012). We present our preliminary experience at a tertiary care center to support this hypothesis. We report 3 patients with moderate to severe anti-TNF experienced CD initiated on ustekinumab therapy, who had minimal response after non-weight based subcutaneous induction; loading with intravenous weight-based Ustekinumab led to clinical and/or endoscopic improvement (Table 1). Patient 1 was a 35-year-old woman with ileocolonic CD with prior intestinal resections and colectomy with ileoanal pouch who had failed multiple anti-TNF therapies and vedolizumab. The patient had improvement in clinical and endoscopic measures after intravenous reloading with ustekinumab. Initiation of ustekinumab combination therapy as well as steroids did not improve disease activity; however, pouchoscopy three months after reloading dose showed improvement in endoscopic disease activity, and the patient was able to wean off corticosteroids. Patient 2 was a 44-year-old man with history of Crohn's ileocolitis with perianal fistulas with prior small bowel resections. The patient was a primary non-responder to Infliximab and did not respond to Vedolizumab combination therapy. He was initiated on ustekinumab combination therapy with improvement in ulceration at the ileocolonic anastomosis; however, he had ongoing abdominal pain, diarrhea, and perianal drainage. After intravenous induction with ustekinumab, his clinical symptoms improved and was able to taper off steroids. Patient 3 was a 26-year-old man with history of ileocolonic Crohn's disease who had secondary loss of response to Infliximab therapy, primary non-response to adalimumab, and was started on ustekinumab combination therapy. He was subsequently hospitalized with an intra-abdominal abscess requiring drainage and antibiotics. After intravenous reinduction of ustekinumab, he had clinical and endoscopic response and successfully tapered off steroids. All 3 patients showed improvement in clinical response after intravenous dosing of ustekinumab with successful tapering of corticosteroids. Endoscopic evaluations showed endoscopic as well as histologic improvement. With further development of therapeutic drug monitoring for ustekinumab, drug concentrations may aid in the use of intravenous loading of ustekinumab, identifying appropriate patients where a rescue dose may augment a sub-optimal response. Based on these preliminary findings, re-induction dosing of ustekinumab in patients on maintenance therapy with sub-optimal clinical response or ongoing steroid dependence may improve outcomes. Prospective studies in patients with Crohn's disease receiving ustekinumab therapy are warranted to elucidate the best approach for optimizing drug therapy.

Efficacy of Tofacitinib in Patients With Ulcerative Colitis by Prior Tumor Necrosis Factor Inhibitor Treatment Status: Results From OCTAVE Induction and Maintenance Studies

Introduction: Many patients (pts) with ulcerative colitis (UC) treated with tumor necrosis factor inhibitors (TNFi) do not respond to initial therapy (primary non-response [NR]) or experience loss of response over time (secondary NR).1 Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated for UC. Methods: Pts in OCTAVE Induction 1 & 2 with moderately to severely active UC who failed or were intolerant to steroids, immunomodulators or TNFi received placebo (PBO; N=234) or tofacitinib 10 mg twice daily (BID; N=905) for 8 weeks (wks). In OCTAVE Sustain, induction study clinical responders were rerandomized to PBO (N=198), tofacitinib 5 mg BID (N=198) or 10 mg BID (N=197) for 52 wks. Corticosteroids were allowed in OCTAVE Induction; corticosteroid taper was mandatory in OCTAVE Sustain. Subgroup analyses by prior TNFi failure status were conducted for remission, mucosal healing and clinical response at Wk 8 (OCTAVE Induction; pooled data) and Wk 52 (OCTAVE Sustain), and sustained steroid-free remission among remitters at baseline of OCTAVE Sustain. Between-group treatment differences and 95% confidence intervals using the normal approximation were calculated, as well as p values based on chi-square test. Results: At Induction baseline, 51.7% of pts had failed TNFi (of whom 55.7% had primary NR, 39.2% secondary NR and 32.6% ≥2 failed TNFi). At Wk 8 of OCTAVE Induction, consistent treatment effects were observed with tofacitinib 10 mg BID vs PBO for all endpoints and categories of prior TNFi treatment status (Table). Observed treatment effects for remission, mucosal healing and clinical response were similar for pts with and without prior TNFi failure, and for pts who failed 1 TNFi and who failed ≥2 TNFi. In OCTAVE Sustain, treatment effects were observed at Wk 52 for 5 mg and 10 mg vs PBO for all endpoints and TNFi treatment categories. Treatment effects in OCTAVE Sustain were generally greater for 10 mg BID vs 5 mg BID, especially in pts with prior TNFi failure.Table: Table. Efficacy in OCTAVE Induction and OCTAVE Sustain Stratified by Prior TNFi Treatment StatusConclusion: Tofacitinib was efficacious vs PBO as induction and maintenance therapy, regardless of prior TNFi failure. Benefits over PBO were apparent even in the most refractory populations, including induction of remission in pts with primary NR, and pts who had failed ≥2 TNFi. Funded by Pfizer Inc. 1. Roda G et al. Clin Trans Gastroenterol 2016:e135.

Invasive mold infections of the central nervous system in patients with hematologic cancer or stem cell transplantation (2000–2016): Uncommon, with improved survival but still deadly often

Historically considered to have very poor outcome, there is paucity of recent data regarding invasive mold infections (IMIs) of the central nervous system (CNS) in patients with hematologic cancer (HC) or stem cell transplantation (SCT). We reviewed the records of HC patients and/or SCT recipients who were diagnosed with CNS IMIs (EORTC/MSG criteria) at MD Anderson Cancer Center (1/1/2000-6/31/2016). Risk factors for survival at day (d) 42 post diagnosis were assessed. We identified 40 such patients (16 with proven infection). The incidence density was 3.8 cases/100000 patient days and mortality remained stable throughout the study period. Most patients had active HC and neutropenia at diagnosis (95% and 53% respectively). Of the 25 patients with a microbiological diagnosis, Aspergillus spp and Mucorales accounted for 85% of cases. CNS IMIs were deemed to be secondary to hematogenous spread in 31 (77%), mostly (90%) fungal pneumonia. CNS lesions typically presented as solitary ring-enhancing abscesses in MRI (26; 65%). Most patients (34; 85%) received lipid AMB and were treated with combination therapy (33; 83%); Mortality 42d was 48%. In univariate analysis, lack of surgical drainage (p=0.01), absence of giant cells (p=0.01) and granulomas (p=0.03) were associated with increased 42d mortality. In multivariate analysis, co-infection was associated with increased (p=0.005), while steroid tapering was associated with decreased mortality (p = 0.01). Although less lethal, improved outcome in these uncommon infections was related only to immune response in histopathology, steroid tapering and possibly surgical drainage. In a contemporary 16-year cohort of 40 patients with hematologic cancer and mold infections of Central Nervous System, 42-day mortality was 48%. Improved survival was related to immune response in histopathology, absence of co-infections, corticosteroid tapering and possibly surgical drainage.

Delirium as presentation of late-onset and relapsing Susac syndrome

A 67-year-old patient, only known for bilateral presbycusis, presented with subacute onset of delirium. Clinical examination showed multifocal neurological deficits, all together suggesting subcortical frontal dysfunction together with cerebellar and...

Urine trouble: genitourinary tuberculosis and subsequent DRESS syndrome

A 40-year-old woman with HIV (CD4 270, viral load undetectable) from Zambia presented with fevers, urinary tract infection symptoms, sterile pyuria and haematuria. She was found to have genitourinary tuberculosis...

Efficacy of Dexamethasone for Acute Primary Immune Thrombocytopenia Compared to Prednisolone: A Systematic Review and Meta-analysis.

Corticosteroids have been established as first-line therapy in acute primary immune thrombocytopenia (ITP), and the clinical guidelines recommend either dexamethasone (Dex) or prednisolone (PSL). The types and dosages of corticosteroids, however, have not yet been determined, because previous randomized control trials (RCTs) comparing Dex and PSL showed controversial results in terms of efficacy. To understand and interpret all available evidence, we conducted a systematic review and meta-analysis of RCTs. The main outcome measure was the incidence of sustained response (SR; platelet count >30 × 10 9 /L for 6 months without concomitant treatments after the completion of the final therapies). Eight RCTs (totaling 704 patients) were included in this study. The incidence of SR showed no significant difference, while it was significantly higher in the Dex arm when used with posttherapy (more than one course of Dex or tapering corticosteroids added; risk ratio [RR], 1.82; 95% confidence interval [CI], 1.38–2.41; p < 0.01). A single course of Dex showed no significant difference. The overall response (platelet >30 × 10 9 /L) at day 28 was significantly improved in the Dex arm (RR, 1.11; 95% CI, 1.01–1.22; p = 0.03) and Dex with posttherapy suppressed long-term relapse (RR of nonevent, 1.32; 95% CI, 1.10–1.59; p < 0.01). There were significantly fewer adverse events in the Dex arm (RR, 0.45; 95% CI, 0.37–0.55; p < 0.01). Use of Dex with posttherapy instead of PSL may be more beneficial as the initial therapy. Studies comparing Dex with other new strategies are essential to determine the most suitable therapeutic regimens for acute ITP.

Clinical features, risk factors and progresses on treatment of recurrent Vogt-Koyanagi-Harada disease

Vogt-Koyanagi-Harada disease(VKH) is a bilateral, granulomatous panuveitis associated with central nervous system, auditory, and integumentary manifestations. Clinically, VKH usually responds well to early aggressive glucocorticosteroid treatment and may be cured without any clinically significant sequelae. Some patients, however, may enter the chronic recurrent phase, which may result in marked loss of vision due to complications such as complicated cataract, secondary glaucoma and maculopathy. Recurrent VKH is mainly characterized by anterior uveitis associated with thickening of the choroid. Initial poor visual acuity, severe anterior chamber reaction, choroidal folds,rapid tapering of systemic corticosteroids or inadequate duration of treatment, and development of extraocular manifestations may be risk factors of disease recurrence. Prolonged glucocorticosteroid treatment has been suggested as effective strategy for recurrence of VKH. The positive effects of other immunosuppressive agents and biologic agents on treatment of chronic recurrent and refractory VKH have been gradually recognized by the uveitis community. (Chin J Ophthalmol, 2017, 53: 317-320).

PERIPHERAL RETINAL VASCULITIS: Analysis of 110 Consecutive Cases and a Contemporary Reappraisal of Tubercular Etiology.

Describe the clinical features and outcomes of patients with peripheral retinal vasculitis (RV) and describe clinical characteristics of presumed tubercular RV in a nonendemic setting. Retrospective cohort study of 110 consecutive patients with peripheral RV at a tertiary referral eye care center in the United Kingdom. Retinal vasculitis was defined as RV with vitritis associated with peripheral retinal ischemia. Patients who also had positive Quantiferon Gold in Tube test, positive tuberculin skin test, and/or other evidence of systemic tuberculosis such as biopsy were labeled with presumed tubercular RV. Treatment success was defined as resolution of inflammation, and successful tapering of oral corticosteroids to less than 10 mg/day or topical steroids to less than twice a day. Mean age of the study population was 42.69 ± 14.95 years. Patients were predominantly Asian (49.1%) and Male (67.0%). A total of 73.2% had bilateral involvement. Sixty-nine (62.72%) patients had presumed tubercular RV. A total of 52.8% patients received antitubercular therapy, 65.5% received oral corticosteroids, and 17.3% required steroid-sparing oral immunosuppressive agents. A total of 85.19% of patients with presumed tubercular RV achieved treatment success with concurrent antitubercular therapy as against 75.61% of patients with nontubercular RV. This is the largest study of the epidemiology, clinical features, and outcomes of both peripheral RV and presumed tubercular RV to date. Presumed tubercular RV commonly seems to affect young males of Asian descent and had vitreous hemorrhage as common clinical findings and also demonstrated a good treatment outcome with antitubercular therapy.

Clinical Characteristics and Outcomes of Patients with Otosyphilis and HIV Infection

BackgroundThe increased rates of syphilis in HIV infected individuals has provided information on ocular and neurological complications, but data on cochleovestibular dysfunction is limited. Otosyphilis is a potentially reversible cause of hearing loss in HIV infected individuals.MethodsWe performed a retrospective chart review from 2007 through 2016 and identified six patients who met inclusion criteria of a diagnosis of otosyphilis and HIV infection. We collected the following data: demographics, clinical characteristics, laboratory findings, treatment courses, and outcomes.ResultsWe identified a total of six patients with HIV and otosyphilis. All patients were male with a mean age of 36 (range 23–51) without known predisposing factors for hearing loss. The mean CD4 count was 323 (range 17–547) with all but two patients having a viral load of less than 50 copies. Four of the patients were receiving combination antiretroviral therapy at the time of diagnosis of otosyphilis. All patients had a rapid plasma reagin (RPR) titer of at least 1:16 (range 1:16–1:128). Three patients presented with unilateral hearing loss and two with bilateral; with one patient having just vestibular dysfunction. The mean duration of symptoms prior to presentation was about seven weeks (range one week to 16 weeks). Three of six patients had objective hearing loss on audiometric testing, one had no detectable hearing loss, and two did not have formal audiometric testing. All had lumbar puncture performed at diagnosis with a CSF mean white blood cell count of 23 (range 0–129) and a mean total protein level of 38 (range 28–57). Only one patient had a positive CSF VDRL test. Five patients were treated with intravenous penicillin for 14 days and one with ceftriaxone for 14 days due to a penicillin allergy. Five patients received a corticosteroid taper. Three out of the six patients noted subjective hearing improvement with treatment in six months.ConclusionHIV infected patients with a diagnosis of syphilis should be asked screening questions to identify hearing symptoms or vestibular dysfunction, as otosyphilis is an important cause of reversible hearing loss.Disclosures All authors: No reported disclosures.

Dexpramipexole As a Steroid-Sparing Agent in Hypereosinophilic Syndromes (HES): An Open-Label Proof-of-Concept Study

Hypereosinophilic syndromes (HES) are a heterogeneous group of disorders characterized by peripheral eosinophilia and eosinophil-related end organ damage. Whereas most patients respond to steroid therapy, high doses are often necessary and serious side effects are common. Dexpramipexole (KNS-760704) is an orally bioavailable synthetic amino-benzothiazole that was in development for the treatment of amyotrophic lateral sclerosis (ALS). Despite failure to meet the primary efficacy endpoint in a phase 3 trial in ALS patients, dexpramipexole showed an excellent safety profile and was found to significantly decrease absolute eosinophil counts (AEC) in >70% of the study participants. Consequently, a proof-of-concept study was designed to evaluate the safety and efficacy of dexpramipexole as a steroid-sparing agent in 10 HES subjects.Subjects with HES on steroid monotherapy were eligible for the study if they required ≥10 mg prednisone or equivalent for control of symptoms and eosinophilia. Subjects with AEC <1000/uL and no active symptoms entered a lead-in period, consisting of a standardized steroid taper with weekly assessment of AEC and symptoms to establish a "minimally effective corticosteroid dose (MECD)". Those with AEC ≥1000/uL entered directly into the treatment phase. Once the MECD was established, treatment with dexpramipexole (150 mg twice daily) was initiated. After 12 weeks of treatment, a standardized corticosteroid taper was attempted to determine the "MECD on dexpramipexole". Clinical assessments, including bone marrow and tissue biopsies of affected organs (when possible), were performed prior to and after 12 weeks of dexpramipexole. The primary efficacy endpoint was defined as a ≥50 % change in prednisone dose to maintain AEC at or below baseline levels and control clinical symptoms.Study enrollment is complete. Median age at enrollment was 51 years (22-72) with 40% women. Baseline clinical manifestations included eosinophilic gastrointestinal disease (60%), pulmonary involvement (50%), skin, muscle, sinus, and cardiac disease. Median baseline AEC was 670/uL (280-2540) and median MECD at baseline was 18.75 mg of prednisone (10-25). To date, the MECD on dexpramipexole has been determined for 7 subjects, and 3 subjects continue on study and have not completed the steroid taper on dexpramipexole. Two of the 7 evaluable subjects met the primary end point. Both subjects reached a MECD of 0 mg of prednisone and had complete symptom resolution with AEC of 0/uL within 3 months of initiating treatment with dexpramipexole. They remain in clinical remission on dexpramipexole monotherapy for 7 and 12 months, respectively. One additional subject who did not meet the primary endpoint at 3 months, was able to maintain a stable dose of 12.5 mg of prednisone with clinical improvement. She has remained on dexpramipexole and has demonstrated a delayed response with AEC 100/uL on 8.75 mg prednisone (50% of her baseline MECD) at 6 months. The remaining 4 evaluable subjects failed to respond and were taken off study. No deaths or drug related adverse events were observed, although 2 subjects reported transient palpitations and insomnia that resolved without drug discontinuation.Bone marrow biopsies performed at 12 weeks revealed markedly decreased AEC and basophils in responders as compared to baseline samples, and residual eosinophils appeared left-shifted. Other cell lineages were unchanged. Gastrointestinal biopsies in 1 responder demonstrated complete resolution of tissue eosinophilia after 5 months on dexpramipexole. Flow cytometry demonstrated no difference in CD34+ or CD34+IL-5R+ cell numbers after 12 weeks of treatment, but a decrease in eosinophil expression of Siglec 8, an inhibitory receptor expressed only on mature eosinophils. These changes were not observed in the non-responders. CD34+ cell cultures using normal cord blood samples also suggest a delay in maturation of the eosinophil lineage in the presence of dexpramipexole.Given the frequency of steroid-induced morbidity in patients with HES, alternate therapeutic options are critical. In this pilot study, dexpramipexole showed remarkable efficacy as a steroid-sparing agent without apparent toxicity in a subset of subjects with steroid-responsive HES. Although the mechanism of action is unknown, preliminary data suggest that dexpramipexole may affect eosinophil maturation in the bone marrow. DisclosuresBozik:Knopp Biosciences: Employment. Brown:Leidos Biomedical Research Inc.: Employment. Demarco:Knopp Biosciences: Employment. Komarov:Knopp Biosciences: Employment. Magee:Leidos Biomedical Research Inc.: Employment. Prussin:Knopp Biosciences: Employment. Signore:Knopp Biosciences: Employment. Sullivan:Knopp Biosciences: Employment. Wetzler:Leidos Biomedical Research Inc.: Employment. Dunbar:Novartis: Research Funding. Dworetzky:Knopp Biosciences: Employment.

Intravitreal Sirolimus for Noninfectious Uveitis: A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA)

To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and120. The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P= 0.025) and 880 μg (16.4%; P= 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P= 0.008) and 880 μg (43.1%; P= 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment.

Impact of intensive treatment and remission on health-related quality of life in early and established rheumatoid arthritis

ObjectivesTo establish if using intensive treatment to reduce synovitis and attain remission in active rheumatoid arthritis (RA) improves all aspects of health-related quality of life (HRQoL).MethodsA secondary analysis of two...

Anti-tuberculous therapy for maintenance of remission in Crohn's disease.

There have been a number of studies with conflicting results which have examined the effect of anti-tuberculous therapy in Crohn's disease. A meta-analysis was performed to evaluate the use of anti-tuberculous therapy for the maintenance of remission in Crohn's disease. To evaluate the effects of anti-tuberculous therapy for the maintenance of remission in patients with Crohn's disease. We searched MEDLINE, EMBASE, the Cochrane LIbrary, and the Cochrane IBD Group Specialized Register from inception to June 22, 2015. Randomized controlled trials (RCTs) of anti-tuberculous therapy compared to placebo or another active therapy in patients with quiescent Crohn's disease were considered for inclusion. At least two authors independently extracted data and assessed the quality of included studies using the Cochrane risk of bias tool. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes.. The primary outcome was relapse. Secondary outcomes included adverse events, withdrawals due to adverse events and serious adverse events. All data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the primary and secondary outcomes was evaluated using the GRADE criteria. Four placebo-controlled RCTs including 206 participants were included. Three trials included an 8 to 16 week induction phase with tapering corticosteroids (prednisone, prednisolone or methylprednisolone) as induction therapy. Anti-tuberculous therapy included monotherapy with clofazimine, combination therapy with clofazimine, rifampin, ethambutol, and dapsone or combination therapy with clarithromycin, rifabutin and clofazimine. All of the studies were rated as unclear risk of bias for allocation concealment, three were rated as unclear risk of bias for random sequence generation and two were rated as unclear risk of bias for blinding or participants and personnel. There was a statistically significant difference in relapse rates favoring anti-tuberculous therapy over placebo. Thirty-nine per cent (44/112) of patients in the anti-tuberculous therapy group relapsed at 9 months to 2 years compared to 67% (63/94) of placebo patients (RR 0.58, 95% CI 0.45 to 0.75, I(2) = 47%). A GRADE analysis indicates that the overall quality of the evidence supporting this outcome was very low due to unknown risk of bias and sparse data. Adverse events occurred more frequently in the anti-tuberculous therapy group (37/159) compared to the placebo group (14/163) with a pooled RR of 2.57 (95% CI 1.45 to 4.55; N=322; studies=4, I(2)=64%). A GRADE analysis indicates that the overall quality of the evidence supporting this outcome was very low due to unknown risk of bias, unexplained heterogeneity and sparse data. There was no difference in withdrawals due to adverse events. Nine per cent (14/159) of anti-tuberculous therapy patients withdrew due to adverse events compared to 7% (11/163) of placebo patients (RR 1.29, 95% CI 0.60 to 2.77, I(2) = 0%). Common adverse events included increased skin pigmentation and rashes. No serious adverse events were reported in any of the included studies. Anti-tuberculous therapy may provide a benefit over placebo for the prevention of relapse in participants with Crohn's disease in remission. However, this result is very uncertain due to unclear study quality and the small numbers of patients assessed. Further studies are needed to provide better quality evidence for the use of anti-tuberculous therapy for maintaining remission in people with quiescent Crohn's disease.

Outcomes of Vogt-Koyanagi-Harada Disease: A Subanalysis From a Randomized Clinical Trial of Antimetabolite Therapies

To report outcomes of Vogt-Koyanagi-Harada (VKH) disease from a clinical trial of antimetabolite therapies. Subanalysis from an observer-masked randomized clinical trial for noninfectious intermediate, posterior, and panuveitis. setting: Clinical practice at Aravind Eye Hospitals, India. Forty-three of 80 patients enrolled (54%) diagnosed with VKH. Patients were randomized to either 25mg oral methotrexate weekly or 1g mycophenolate mofetil twice daily, with a corticosteroid taper. Primary outcome was corticosteroid-sparing control of inflammation at 5 and 6months. Secondary outcomes included visual acuity, central subfield thickness, and adverse events. Patients were categorized as acute (diagnosis ≤3months prior to enrollment) or chronic (diagnosis >3months prior to enrollment). Twenty-seven patients were randomized to methotrexate and 16 to mycophenolate mofetil; 30 had acute VKH. The odds of achieving corticosteroid-sparing control of inflammation with methotrexate were 2.5 times (95% CI: 0.6, 9.8; P= .20) the odds with mycophenolate mofetil, a difference that was not statistically significant. The average improvement in visual acuity was 12.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. On average, visual acuity for patients with acute VKH improved by 14 more ETDRS letters than those with chronic VKH (P < .001), but there was no difference in corticosteroid-sparing control of inflammation (P= .99). All 26 eyes with a serous retinal detachment at baseline resolved, and 88% achieved corticosteroid-sparing control of inflammation. The majority of patients treated with antimetabolites and corticosteroids were able to achieve corticosteroid-sparing control of inflammation by 6months. Although patients with acute VKH gained more visual improvement than those with chronic VKH, this did notcorrespond with a higher rate of controlled inflammation.

PWE-020 Corticosteroid Dose Reduction with Vedolizumab Treatment of Crohn’s Disease: Abstract PWE-020 Table 1

Introduction Corticosteroids (CS) can effectively induce remission of Crohn’s disease (CD), but serious side effects prohibit long-term use. Vedolizumab (VDZ) maintenance therapy resulted in a significantly higher percentage of patients with CS-free remission at week 52 versus placebo (PBO) in the GEMINI 2 study of moderately to severely active CD. 1 Methods In GEMINI 2, patients who responded to VDZ induction therapy at week 6 were re-randomised to PBO or VDZ for 46 weeks. From week 6 onward, patients with clinical response began a CS tapering regimen. With exploratory and post hoc analyses, we characterised CS dose reductions following VDZ therapy in the population of patients on stable CS doses (≤30 mg/day prednisone or equivalent) at baseline (week 0). Median CS dose over time, change from baseline CS dose, and CS-free status at week 52 were summarised overall and by tumour necrosis factor antagonist (anti-TNF) treatment (naive or failure) history. Results At week 52, 68% of patients with baseline CS use decreased their CS dose with VDZ treatment compared with 62% with PBO ( Table ). The median CS dose in either treatment group (VDZ or PBO) at week 52 was 5 mg/day. Higher percentages of patients (overall and anti-TNF-naive) required CS doses of ≤7.5 mg/day with VDZ versus PBO at week 52 ( Table ). In anti-TNF-naive patients, the median CS dose at week 52 was 2.7 mg/day with VDZ and 5.0 mg/day with PBO. At week 52, higher percentages of VDZ-treated patients were CS- free for 90 or 180 consecutive days than PBO-treated patients. Conclusion VDZ maintenance therapy was associated with numerically higher percentages of CS-free patients at week 52 and patients who were CS-free for 90 or 180 days than PBO. Interpretation of these post hoc analyses, including the degree of dose reduction, is limited by differing initiation weeks for CS tapering per patient and small sample sizes. Reference 1 Sandborn WJ, et al . N Engl J Med . 2013; 369 :711–721; NCT00783692 . Disclosure of Interest E. Loftus Jr Grant/research support from: AbbVie, Janssen, UCB, Takeda, Pfizer, GSK, Amgen, BMS, Genentech, Robarts Clinical Trials, Gilead, Receptos, Consultant for: AbbVie, Janssen, UCB, Takeda, Immune Pharmaceuticals, Celgene, MedImmune, Theradiag, Genentech, Seres Health, Sun Pharmaceuticals, BMS, C. Siegel Grant/research support from: AbbVie, Janssen, Salix, Takeda, UCB, Consultant for: AbbVie, Amgen, Janssen, Lilly, Pfizer, Takeda, UCB, Speaker bureau with: AbbVie, Janssen, Takeda, R. Panaccione Grant/research support from: Abbott, and UCB Inc, Consultant for: Abbott, Biogen, Axcan Pharma Inc, BMS, Centocor Inc, Chemocentryx, Ferring, Genentech Inc, Lippincott Williams & Wilkins, Medscape, Osiris Therapeutics, Inc, Novartis, Genentech Inc, Elan Pharmaceuticals, Inc, UCB, W. Sandborn Grant/research support from: Janssen, AbbVie, Pfizer, Amgen, Genentech, Consultant for: Janssen, AbbVie, Pfizer, Amgen, Genentech, Takeda, Speaker bureau with: AbbVie, Takeda, M. Smyth Employee of: Takeda Development Centre Europe Ltd, London, UK, A. James Employee of: Takeda Development Centre Europe Ltd, London, UK, J. Xu Employee of: Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, USA, B. Abhyankar Employee of: Takeda Development Centre Europe Ltd, London, UK

PTH-072 Corticosteroid Dose Reduction in Ulcerative Colitis Patients Treated with Vedolizumab: Abstract PTH-072 Table 1

Introduction Corticosteroids (CS) are effective for the short-term treatment of patients (pts) with ulcerative colitis (UC), but serious side effects prohibit long-term use. In the GEMINI 1 study, a higher percentage of pts with moderately to severely active UC were in CS-free remission at week (wk) 52 with vedolizumab (VDZ) treatment than with placebo (PBO). 1 Methods In GEMINI 1, pts who responded to VDZ induction therapy at wk 6 were re-randomised to PBO or VDZ for 46 wks. From wk 6 onward, pts with clinical response discontinued CS use. We characterised CS dose reductions achieved with VDZ therapy in exploratory and post hoc analyses of pts with baseline (wk 0) CS use (≤30 mg/day prednisone or equivalent). Median CS dose over time, change from baseline CS dose, and CS-free status at wk 52 were summarised overall and by anti-tumour necrosis factor (anti-TNF) treatment (naive or failure) history. Results Of pts with baseline CS use, 74% decreased their CS dose with VDZ treatment at week 52 (vs 57% with PBO) (Table). At wk 52, 56% of VDZ-treated pts were on ≤7.5 mg/day of CS ( Table ), and the median CS dose was 2.5 mg/day for VDZ-treated pts and 10.0 mg/day for PBO. Numerically higher percentages of VDZ-treated pts were CS-free for 90 and 180 consecutive days at wk 52 than PBO- treated pts. Similar trends were observed in the anti-TNF-naive and anti-TNF-failure populations. Conclusion Numerically greater reductions in CS use were achieved with VDZ maintenance therapy compared with PBO. At week 52, VDZ therapy was associated with numerically higher percentages of CS-free patients and patients who were CS-free for 90 or 180 consecutive days than PBO. Interpretation of these post hoc analyses, including the degree of dose reduction, is limited by differing initiation weeks for CS tapering per patient and small sample sizes. Reference 1 Feagan BG, et al . N Engl J Med . 2013; 369 :699–710; NCT00783718. Disclosure of Interest E. Loftus Jr Grant/research support from: from AbbVie, Janssen, UCB, Takeda, Pfizer, GlaxoSmithKline, Amgen, Bristol-Myers Squibb, Genentech, Robarts Clinical Trials, Gilead, Receptos, Consultant for: AbbVie, Janssen, UCB, Takeda, Immune Pharmaceuticals, Celgene, MedImmune, Theradiag, Genentech Inc, Seres Health, Sun Pharmaceuticals, Bristol-Myers Squibb, C. Siegel Grant/research support from: AbbVie, Janssen, Salix, Takeda, UCB, Consultant for: AbbVie, Amgen, Janssen, Lilly, Pfizer, Takeda, UCB, Speaker bureau with: AbbVie, Janssen, Takeda, R. Panaccione Grant/research support from: Abbott, and UCB Inc, Consultant for: Abbott, Biogen/IDEC, Axcan Pharma Inc, Bristol-Myers Squibb, Centocor, Inc, Chemocentryx, Ferring Pharmaceuticals Inc, Genentech Inc, Lippincott Williams & Wilkins, Medscape, Osiris Therapeutics, Inc, Novartis Pharmaceuticals, Genentech Inc, Elan Pharmaceuticals, Inc, UCB, Inc, W. Sandborn Grant/research support from: Janssen, AbbVie, Pfizer, Amgen, Genentech, Consultant for: Janssen, AbbVie, Pfizer, Amgen, Genentech, Takeda, Speaker bureau with: AbbVie, Takeda, M. Smyth Employee of: Takeda Development Centre Europe Ltd, London, UK, A. James Employee of: Takeda Development Centre Europe Ltd, London, UK, J. Xu Employee of: Takeda Pharmaceuticals International Co, Cambridge, Massachusetts, USA, B. Abhyankar Employee of: Takeda Development Centre Europe Ltd, London, UK

A Case of Eales Disease in Postpartum Period

A 31-year-old female presented with visual field defect and floaters in right eye. Symptom occurred just before labor and worsened after labor. The best corrected visual acuity was 1.0 in the right eye. Fundus examination revealed retinal hemorrhage and periphlebitis in the affected eye. After 2 weeks, newly developed retinal vasculitis was observed in the fellow eye as well as in the affected eye. She was treated with systemic corticosteroid and disease activity increased while tapering corticosteroid. After adding systemic immunomodulating agent, disease activity was controlled. Retinal neovascularization was observed in previous non-perfusion area. She underwent vitrectomy in the right eye due to recurrent vitreous hemorrhage, and prophylactic laser photocoagulation was performed in the left eye.

Year in review 2015: Interstitial lung disease, pulmonary vascular disease, pulmonary function, sleep and ventilation, cystic fibrosis and paediatric lung disease.

Keywords: interstitial lung disease; lung function; paediatric lung disease; pulmonary vascular disease; sleep