Long-term Immunomodulatory Therapy Research Articles

Update on Sympathetic Ophthalmia

Abstract Sympathetic ophthalmia (SO) is a rare bilateral diffuse granulomatous intraocular inflammation, which occurs days or months following surgery or trauma to one eye. After penetrating ocular injuries and during intraocular surgery, the incidence of SO varies from 0.2% to 0.5% and 0.01%, respectively. Other risk factors include cyclodestructive operations and vitreoretinal surgery. With 80% of cases appearing within three months following injury to the exciting eye and 90% occurring within one year, the temporal interval between ocular injury and the onset of SO varies widely, ranging from a few days to decades. The diagnosis is based on clinical findings. It manifests as bilateral diffuse uveitis. In the sympathetic, uninjured eye, patients describe a sneaky beginning of blurred vision, discomfort, epiphora and photophobia. Typically, this is accompanied by conjunctival injection and a granulomatous anterior chamber reaction, resulting in mutton fat keratic precipitates (KPs). The degree of inflammation in the posterior chamber can differ. One of the initial lines of treatment for SO is systemic corticosteroids. Long-term immunomodulatory therapy may involve azathioprine, mycophenolate mofetil, cyclosporine or other immunosuppressive drugs if patients do not respond to steroid therapy or if their side effects are clinically substantial.

Vision Outcomes of Long-Term Immunomodulatory and Steroid Therapy in Sympathetic Ophthalmia

To compare vision acuity outcomes of long-term steroid therapy compared with immunomodulatory therapy for treatment of sympathetic ophthalmia. Single-center, retrospective, comparative clinical study. Patients with sympathetic ophthalmia treated from March 2005 to October 2022 with at least 1 year of follow-up were included. Visual acuity outcomes were compared by steroid and immunomodulatory treatment modality. Thirty-five patients with sympathetic ophthalmia were included in the study, with follow-up ranging from 1 to 17 years. Higher rates of vision loss correlated with longer periods of active uveitis and steroid treatment. Lower rates of vision loss correlated with longer periods of uveitis remission on immunomodulatory therapy alone and drug-free remission. Treatment with alkylating agents or combination therapy with an antimetabolite, a biologic-response modifier, and cyclosporine are more likely to result in sympathetic ophthalmia remission. Immunomodulatory therapy leads to superior vision outcomes in cases of steroid-resistant or recurrent sympathetic ophthalmia. Steroid therapy may be useful for acute or recalcitrant sympathetic uveitis but is insufficient for long-term inflammatory control. PRéCIS: This manuscript describes a retrospective analysis of vision outcomes in patients with sympathetic ophthalmia. Results indicate that long-term immunomodulatory therapy is associated with better vision outcomes than long-term steroid therapy for sympathetic ophthalmia treatment.

Visual outcome in pediatric uveitis: A retrospective data review in 277 children.

This study aimed to describe visual outcomes in cases of pediatric uveitis in an Indian population and to analyze various factors affecting these outcomes. Single-center, retrospective chart review of 277 cases of uveitis in patients under the age of 18 years. Variables assessed included age and sex distribution, anatomical location of uveitis, systemic associations, complications, and various treatment strategies used, including long-term immunomodulation and surgical management of complications if required. The main outcome was the final visual acuity. At the final visit, 51.5% of the eyes showed improvement in the final visual acuity, while vision remained stable in 28.7% and 19.7% of the eyes showed worsening of vision at the final follow-up. A total of 19.4% of patients were blind in at least one eye at the final visit, and 16 patients (5.77%) remained bilaterally blind at the final follow-up. The presence of cataract (p = 0), posterior uveitis (p = 0.005), and retinal detachment (p = 0.014) were the most significant risk factors for predicting worse visual outcomes. More than half (65.7%) of patients reported a complication at some point in their follow-up, and the most common complication was cataract. In total, 50.9% of patients required long-term immunomodulatory therapy. Pediatric uveitis remains a challenging condition to treat and follow-up, and the visual outcome remains guarded for most patients.

Efficacy and safety of adalimumab for inflammatory flare prevention in paediatric non-infectious anterior uveitis with peripheral retinal vascular leakage: a study protocol for a single-centre, randomised controlled trial

IntroductionPaediatric patients with chronic anterior uveitis are more prone to suffer from the chronic course of intraocular inflammation and adverse effects of long-term immunomodulatory therapy, either topical glucocorticosteroids or systemic...

O01 Post-transplant lymphoproliferative disorder (PTLD) in a patient with rheumatoid arthritis

O01 Post-transplant lymphoproliferative disorder (PTLD) in a patient with rheumatoid arthritis

P-153: Is it time for a more holistic approach to the treatment of Multiple Myeloma?

P-153: Is it time for a more holistic approach to the treatment of Multiple Myeloma?

Застосування азитроміцину в клінічній практиці

Азитроміцин є антибіотиком, який зазвичай призначається для лікування інфекцій верхніх і нижніх дихальних шляхів у дітей. Незважаючи на його високу популярність, останніми роками збільшились побоювання щодо зростаючої резистентності збудників респіраторних захворювань до цього препарату. Розглянуто фармакокінетику, спектр активності, проблему стійких бактерій і клінічні аспекти, а також рекомендації щодо застосування. Азитроміцин рекомендується як антибіотик вибору для емпіричної й селективної терапії основних бактеріальних збудників гострих кишкових інфекцій у дітей, для етіотропного лікування коклюшу, при хворобі Лайма та для тривалої імуномодулюючої терапії при муковісцидозі.

Pulse oral corticosteroids in pediatric chronic inflammatory demyelinating polyneuropathy.

Childhood onset chronic inflammatory demyelinating polyneuropathy (CIDP) often requires long-term immunomodulatory therapy. We report a comprehensive review of our treatment of pediatric CIDP with a focus on high-dose weekly corticosteroids ("pulse oral corticosteroids"), a treatment method that is not commonly reported. We retrospectively reviewed medical records of pediatric patients with CIDP treated at our center between 2000 and 2018 for whom we had at least 12 mo follow-up. Here, we describe the demographics, disease course, treatment regimens, and long-term outcomes of these patients. Twenty-five patients were identified for analysis. Pulse oral corticosteroid monotherapy was the predominant maintenance treatment in 56% of patients. Patients were followed for a median of 4 y. Side effects were seen in a minority of patients. The probability of a normal exam or being off treatment at last follow-up was similar regardless of predominant maintenance therapy. Pulse oral corticosteroid therapy is a safe and effective long-term treatment option in children with CIDP.

Long-term safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis: Results from the TOWER extension study

BackgroundIn the phase 3 TOWER core study (NCT00751881), the efficacy and safety of teriflunomide compared with placebo were demonstrated in patients with relapsing forms of multiple sclerosis (RMS). Here, the long-term safety and efficacy outcomes from the TOWER extension study (NCT00751881) are reported. MethodsAll patients who entered the extension (N = 751) were assigned to teriflunomide 14 mg and assessed for long-term safety and efficacy. ResultsOf 751 patients in the TOWER extension study, 253, 265, and 233 patients received placebo/teriflunomide 14 mg, teriflunomide 7 mg/14 mg, and teriflunomide 14 mg/14 mg, respectively. Median teriflunomide exposure was 4.25 years (maximum 6.3 years). The overall frequency of adverse events (AEs) was comparable across treatment groups, but a higher proportion of patients in the teriflunomide 7 mg/14 mg (12.4%) and 14 mg/14 mg (12.4%) groups had serious AEs compared with the placebo/teriflunomide 14 mg group (6.4%). Alanine aminotransferase increase and hair thinning occurred at a higher frequency in the placebo/teriflunomide 14 mg group (11.2% and 14.3%, respectively) compared with the teriflunomide 7 mg/14 mg (3.0% and 4.5%, respectively) and 14 mg/14 mg groups (5.2% and 4.3%, respectively). The incidences of AEs of interest (hematologic and hepatic effects, peripheral neuropathy, hypertension, and malignancy) were low and comparable across treatment arms. Disability worsening and adjusted annualized relapse rates were low and stable over time, and mean Expanded Disability Status Scale scores were unchanged over time, for all treatment groups. ConclusionIn the TOWER extension study, the efficacy of teriflunomide 14 mg was maintained in patients with RMS. No new or unexpected AEs were observed with teriflunomide treatment, supporting a safety profile in the extension that was consistent with the core trial. These findings support the positive benefit:risk profile of teriflunomide as a long-term immunomodulatory therapy.

Risk of COVID-19 in dermatologic patients receiving long-term immunomodulatory therapy

Risk of COVID-19 in dermatologic patients receiving long-term immunomodulatory therapy

Reliability of Conjunctival Biopsy for Diagnosis of Ocular Mucous Membrane Pemphigoid: Redetermination of the Standard for Diagnosis and Outcomes of Previously Biopsy-Negative Patients

ABSTRACT Purpose: To demonstrate the reliability of conjunctival biopsy analyzed by direct immunofluorescence (DIF) and supplemented with avidin-biotin complex immunoperoxidase (ABC) in diagnosing oMMP, and report therapy response in biopsy-positive patients, particularly when previously biopsy-negative elsewhere. Methods: Retrospective outcomes review of 136 consecutive patients after conjunctival biopsy for suspected oMMP. Results: Among 136 patients, 66% were diagnosed with oMMP by DIF and 13% via supplemental ABC immunoperoxidase. Sensitivity increased from 79.6% with DIF to 95.6% with supplemental ABC. Among 57 biopsy-positive patients, 77% were in remission at 1-year follow-up and 88% after 2 years. Of 34 previous biopsy-negative but now biopsy-positive patients with a 2-year follow-up, 91% achieved remission, including all 16 diagnosed via DIF and ABC. Conclusion: Conjunctival biopsy analyzed by histopathology and DIF supplemented by ABC has high reliability for diagnosing oMMP and is a useful tool to use before starting long-term immunomodulatory therapy in a patient with suspected oMMP.

Serial Anti–Myelin Oligodendrocyte Glycoprotein Antibody Analyses and Outcomes in Children With Demyelinating Syndromes

Identifying the course of demyelinating disease associated with myelin oligodendrocyte glycoprotein (MOG) autoantibodies is critical to guide appropriate treatment choices. To characterize serial anti-MOG antibody serologies and clinical and imaging features at presentation and during follow-up in an inception cohort of prospectively monitored children with acquired demyelination. In this prospective cohort study, study participants were recruited from July 2004 to February 2017 through the multicenter Canadian Pediatric Demyelinating Disease Study. Inclusion criteria included (1) incident central nervous system demyelination, (2) at least 1 serum sample obtained within 45 days from onset, and (3) complete clinical information. Of 430 participants with acquired demyelinating syndrome recruited, 274 were included in analyses. Of 156 excluded participants, 154 were excluded owing to missing baseline samples and 2 owing to incomplete clinical information. Data were analyzed from May to October 2018. Presence of anti-MOG antibodies was blindly assessed in serial samples collected over a median of 4 years. Clinical, magnetic resonance imaging, and cerebrospinal fluid features were characterized at presentation, and subsequent disease course was assessed by development of new brain magnetic resonance imaging lesions, total lesion volume at last evaluation, annualized relapse rates, Expanded Disability Status Scale score and visual functional score at 4 years, and any disease-modifying treatment exposure. Of the 274 included participants, 140 (51.1%) were female, and the median (interquartile range) age of all participants was 10.8 (6.2-13.9) years. One-third of children were positive for anti-MOG antibodies at the time of incident demyelination. Clinical presentations included a combination of optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis for 81 of 84 anti-MOG antibody-positive children (96%). Brain lesions were present in 51 of 76 anti-MOG antibody-positive participants (67%), but magnetic resonance imaging characteristics differed with age at presentation. Complete resolution of baseline lesions was observed in 26 of 49 anti-MOG antibody-positive participants (53%). On serial serum analysis, 38 of 67 participants (57%) who were seropositive at onset became seronegative (median time to conversion, 1 year). Among all participants who were positive for anti-MOG antibodies at presentation, clinical relapses occurred in 9 of 24 children (38%) who remained persistently seropositive and in 5 of 38 children (13%) who converted to seronegative status. Myelin oligodendrocyte glycoprotein antibodies are common in children with acquired demyelinating syndrome and are transient in approximatively half of cases. Even when persistently positive, most anti-MOG antibody-positive children experience a monophasic disease. The presence of anti-MOG antibodies at the time of incident demyelination should not immediately prompt the initiation of long-term immunomodulatory therapy.

Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach

To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts. Modified Delphi process. A survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement. There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies. Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.

Longterm immunomodulatory therapy in 4.938 outpatients with relapsing-remitting multiple sclerosis (RRMS) under special consideration of switching to oral DMD

Longterm immunomodulatory therapy in 4.938 outpatients with relapsing-remitting multiple sclerosis (RRMS) under special consideration of switching to oral DMD

Update on sympathetic Ophthalmia

Sympathetic ophthalmia (SO) is a bilateral diffuse granulomatous intraocular inflammation that occurs in most cases within days or months after surgery or penetrating trauma to one eye. The incidence of SO ranges from 0.2 to 0.5% after penetrating ocular injuries and 0.01% after intraocular surgery. Vitreoretinal surgery and cyclodestructive procedures are considered risk factors. The time from ocular injury to onset of SO varies greatly, ranging from a few days to decades, with 80% of the cases occurring within 3 months after injury to the exciting eye and 90% within 1 year. The diagnosis is based on clinical findings rather than on serological testing or pathological studies. It presents as a bilateral diffuse uveitis. Patients report an insidious onset of blurry vision, pain, epiphora, and photophobia in the sympathizing, non-injured eye. Classically this is accompanied by conjunctival injection and a granulomatous anterior chamber reaction with mutton-fat keratic precipitates (KPs) on the corneal endothelium. In the posterior segment, the extent of inflammation can vary. Systemic corticosteroids are the first line therapy for SO. If patients are non-responsive to steroid therapy or have clinically significant side effects, cyclosporine, azathioprine or other immunosuppressive agents can be used for long-term immunomodulatory therapy.

Management of uveitic glaucoma with Ahmed glaucoma valve implantation

Objective To evaluate the safety and efficacy of Ahmed glaucoma valve implantation for the management of glaucoma associated with chronic uveitis. Design Retrospective, noncomparative case series. Participants Nineteen patients (21 eyes) with chronic uveitis underwent Ahmed glaucoma valve implantation for uncontrolled glaucoma between 1995 and 1998. Intervention All patients had their uveitis controlled before surgery via immunomodulatory therapy. Ahmed glaucoma valve implantation was performed. Immunosuppression was continued in the early postoperative period for strict control of inflammation. Main outcome measures Control of intraocular pressure (IOP). A secondary outcome measure was the number of antiglaucoma medications required to achieve the desired IOP. Visual acuity and complications associated with the surgery were monitored. Results The postoperative follow-up averaged 24.5 months. At the most recent visit, all 21 eyes had IOPs between 5 and 18 mmHg. The average pressure reduction after Ahmed glaucoma valve implantation was 23.7 mmHg. The average number of antiglaucoma medicines required to achieve the desired IOP was reduced from 3.5 before surgery to 0.6 after surgery. No eye lost even a single line of Snellen acuity at the most recent postoperative visit. Two eyes developed hypotony in the course of follow-up. One resolved without specific intervention, and the other eye required two autologous blood injections and tube ligature to correct the hypotony. One eye underwent Ahmed glaucoma valve replacement for abrupt valve failure. Two eyes underwent penetrating keratoplasty for reasons believed to be unrelated to the glaucoma surgery. Kaplan-Meier life-table analysis showed a cumulative probability of success after Ahmed glaucoma valve implantation of 94% at 1 year. Conclusions Ahmed glaucoma valve implantation can be an effective and safe method in the management of uveitic glaucoma. The authors hypothesize that control of the patients’ uveitis, through preoperative and long-term postoperative immunomodulatory therapy, may have contributed to the success rate reported herein.

Chronic Inflammatory Demyelinating Polyneuropathy.

Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) requires long-term immunomodulatory therapy, which has potential side effects. Before such therapy is instituted, a firm diagnosis of CIDP must be established. Prednisone, plasma exchange (PE), and intravenous immunoglobulin (IVIG) are all proven first-line therapies for CIDP that are of similar efficacy. The choice of treatment should be individualized based on costs, availability, and potential adverse effects. Except in the elderly and in those with complicating medical illnesses, IVIG is well tolerated and easy to administer; hence, it should be the initial therapy for most patients with CIDP. Because of its prohibitive costs and limited availability, however, it is not ideal for long-term administration. In the elderly and in those with complicating medical illnesses (eg, diabetes, obesity, or hypertension), PE may be used as the first-line therapy. Because the effects of PE are transient and because it is expensive, requires vascular access, and can only be performed in specialized centers, long-term therapy with PE alone is problematic. Prednisone is inexpensive, easily available, and of proven efficacy. It is the preferred treatment in young, otherwise healthy persons either as a first-line therapy or in association with IVIG or PE. Patients who require repeated treatment with IVIG or PE and cannot tolerate prednisone or those who require high-dose prednisone should be administered azathioprine, cyclosporin A, or cyclophosphamide, usually in combination with one of the first-line therapies.