Clinical Characteristics and Efficacy of Adalimumab and Low-Dose Methotrexate Combination Therapy in Patients With Vogt–Koyanagi–Harada Disease

This retrospective study investigated the clinical characteristics and efficacy of adalimumab and low-dose methotrexate combination therapy in patients with Vogt–Koyanagi–Harada disease who were treated at Hiroshima University from February 2012 to May 2021. The patients' demographics, clinical features at administration of immunosuppressive therapy, steroid-sparing immunosuppressive therapy, side effects, and relapses were recorded. The efficacies of steroid-sparing immunosuppressive therapy (methotrexate, cyclosporine A, adalimumab, and adalimumab and methotrexate combination therapy) were analyzed. Among 62 patients, the median age at diagnosis was 47 years and the median duration of uveitis was 51 months. Systemic corticosteroid therapy was administered to 93.5% of patients (n = 58). Thirty-four patients (54.8%) were treated with steroid-sparing immunosuppressive therapy. Methotrexate and cyclosporine A were administered to 12 and 22 patients, respectively; relapse occurred in 50.0% and 22.7% of the patients, respectively. Discontinuation of cyclosporine A was required in 63.6% of patients because of side effects. Adalimumab was administered to 14 patients. Recurrence occurred in 11 patients, requiring methotrexate concomitantly. The mean dose of methotrexate at inflammatory quiescence after side effect-related dose decrease was 8.0 mg/week (0.13 mg/kg). The median duration of combination therapy without recurrence was 20 months. There were no serious adverse events during adalimumab therapy. A high relapse rate was observed in patients receiving methotrexate; a high rate of side effects requiring discontinuation was observed in patients receiving Cyclosporine A. Patients with late-stage Vogt–Koyanagi–Harada disease may achieve better control with adalimumab and methotrexate combination therapy.

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OP0224 Similar short term clinical response to initial treatment with high versus low dose methotrexate in mono- and combination therapy in early rheumatoid arthritis patients

10.1136/annrheumdis-2017-eular.1601 ◽

2017 ◽

Author(s):

SA Bergstra ◽

CF Allaart ◽

R van den Berg ◽

A Chopra ◽

N Govind ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Combination Therapy ◽

Clinical Response ◽

Early Rheumatoid Arthritis ◽

Initial Treatment ◽

Low Dose ◽

Short Term ◽

Dose Methotrexate

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Side Effects of Low-Dose Methotrexate

Annals of Internal Medicine ◽

10.7326/p20-0001 ◽

2020 ◽

Vol 172 (6) ◽

pp. I-20

Keyword(s):

Side Effects ◽

Low Dose ◽

Dose Methotrexate

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Low-Dose Methotrexate as Salvage Therapy for Refractory Graft-Versus-Host Disease (GVHD) after Reduced-Intensity Conditioning (RIC) for Allogeneic Stem Cell Transplantation (allo-SCT).

Blood ◽

10.1182/blood.v106.11.1802.1802 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1802-1802

Author(s):

Mohamad Mohty ◽

Hugues de Lavallade ◽

Catherine Faucher ◽

Sabine Furst ◽

Jean El-Cheikh ◽

...

Keyword(s):

Side Effects ◽

Salvage Therapy ◽

Low Dose ◽

Acute Gvhd ◽

Chronic Gvhd ◽

High Risk Population ◽

High Morbidity ◽

Dose Methotrexate ◽

Grade 3

Abstract Background. RIC regimens are increasingly used for allo-SCT. Although such regimens are associated with a relatively low early transplant-related mortality (TRM) in comparison to standard myeloablative allo-SCT, GVHD remains a matter of concern. Of note, corticosteroid-resistant GVHD is associated with high morbidity and mortality, and therapeutic options are limited for those patients. Furthermore, patients undergoing RIC allo-SCT are older than patients undergoing myeloablative allo-SCT, and are thus more exposed to the side effects and complications of long term corticosteroids (CS) administration. Low dose methotrexate (MTX) therapy is a well established modality for prophylaxis of GVHD after standard myeloablative allo-SCT. However, little is known about the role of this drug in the treatment of CS-resistant GVHD. Patients and Methods. The aim of this pilot single center study was to investigate the role and benefit of MTX in a curative setting after failure of CS treatment in 20 consecutive patients undergoing RIC allo-SCT. 20 patients experiencing severe GVHD received IV infusions of low dose MTX (5 mg/m2/infusion) at weekly intervals, for at least four weeks. Reasons for MTX administration were: refractory acute GVHD (after at least one week of 2 mg/Kg CS administration), CS-refractory chronic GVHD, chronic GVHD exacerbation after CS taper, or CS side effects and complications (CS-induced diabetes requiring insulin therapy, severe metabolic or psychiatric disorders). Responses to low dose MTX infusions were assessed one month after the last infusion in each involved organ. Results. 12 patients were treated for severe acute GVHD, while 8 patients received MTX for extensive chronic GVHD. Median age of patients was 51 (range, 22–60). Median time of administration of MTX was day +89 (range, 32–300) after allo-SCT. Of note, none of the patients received any other concomitant therapy for refractory GVHD. 13 patients responded to MTX administration (65 %) with 5 complete responses (25%). Among the 12 patients treated for acute GVHD, 7 responded (58%) of whom 5 CRs (42%). 3 patients did not respond and died from resistant GVHD. Interestingly, 5 patients from the group of grade 3–4 acute GVHD responded. Among the 8 patients treated for chronic GVHD, 6 were responders (75%). In addition, MTX allowed a significant reduction of CS daily dosage ranging from 25% to 80%, as assessed one month after the last administration of MTX. With a median follow-up of 287 days, no increase of CS therapy was necessary among these 6 MTX-responding patients. In the whole study population, toxicity of low dose MTX administration was low (transient and mild reversible cytopenia in 3 cases, 15%). Among the 20 patients, 14 are still alive (70%) with a median follow-up of 293 (range, 65–513) days. Overall, 2 patients died of progressive disease, while 4 patients died from refractory GVHD. Conclusions. In this study, the global response rate of severe GVHD to low dose MTX was impressively high (65%) if considered in terms of salvage therapy in this relatively elderly and high risk population. Low dose MTX appears to be a well-tolerated, inexpensive and likely steroid-sparing agent that is worthy of further investigation in prospective trials for treatment of refractory GVHD, but also as frontline therapy in combination with CS.

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Low Dose and Standard Dose of Imatinib Therapy for Patients with Chronic Myeloid Leukemia in Akita Prefecture, Japan.

Blood ◽

10.1182/blood.v110.11.4575.4575 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4575-4575

Author(s):

Naoto Takahashi ◽

Yoshihiro Kameoka ◽

Hirofumi Saitoh ◽

Naohito Fujishima ◽

Makoto Hirokawa ◽

...

Keyword(s):

Side Effects ◽

Clinical Characteristics ◽

Low Dose ◽

Standard Dose ◽

Point Mutations ◽

Imatinib Therapy ◽

Group I ◽

Akita Prefecture ◽

Group 2 ◽

Group 1

Abstract The IRIS study for CML patients demonstrated the excellent clinical and cytogenetic/molecular effects of imatinib. Patients participating in the IRIS trial were selected according to strict eligibility criteria. The clinical features of patients are usually much more heterogeneous in practical situations than in clinical trials. Sometimes, patients cannot be treated with the standard dose of imatinib because of severe toxicity, especially older patients or patients who had already been treated with the other drugs. In this study, we analyzed whether patients could still be effectively treated using lower doses. Our study analyzed 86 CML patients from 17 hospitals in Akita prefecture. 80 patients were in CP, one patient was in AP, 4 patients were in BC, and one patient had cytogenetic relapse after allo-SCT. All patients were treated with imatinib between December 2001 and July 2007. Initially a dose of 400mg/day was given to almost all patients. Later the dose was decreased in a subset of patients experiencing imatinib-induced side effects. We classified patients into two groups according to the imatinib dosage and analyzed their clinical characteristics [Table 1] and the accumulation of CCR/MMR [Figure 1, 2]. In Group 1, we analyzed 55 patients received 300mg or more of imantiib per day. In Group 2, we analyzed 31 patients received less than 300mg of imatinib per day. Patients in Group 2 were older and had more histories of pretreatment and showed a higher frequency of adverse effects of imatinib than in Group 1. There were no significant differences of CCR/MMR rate between Group 1 and Group 2. This study reproduces the imatinib efficacy results described in the IRIS study, not only for patients treated with standard dose imatinib and for patients who could not take 400mg/day because of imatinib toxicity or other complications. We did not observe an increase in frequency of BCR-ABL point mutations in patients receiving a lower dose of imatinib, suggesting that the low dose imatinib treatment analyzed in our study does not enhance imatinib resistance by increasing BCR-ABL point mutations. In conclusion, we provide data supporting the use of lower doses of imatinib for CML patients that cannot be given sufficient dosage of imatinib for reasons such as severe hematological or non-hematological side effects or other complication. Clinical Characteristics of Patients in Group I and II Group 1(n=55) Group 2(n=31) P Average doseage 380 mg/day 185 mg/day Average age (% of over 70 yrs) 57.7 yrs (22 %) 68.0 yrs (58 %) .001 (.007) History of treatment with IFN/HU before imatinib therapy 16% 55%. 002 Adverse effect (Grade3/4) 16% 42% .009 PFS to AP/BC at 60 Mo 97.8% 89.6% .28 CCR /MMR rate 78% / 51% 61% / 39% .09 / .27 Point mutation of bcr-abl in patients without MMR 4/17 2/13 .99 Figure Figure Figure Figure

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Similar short-term clinical response to high-dose versus low-dose methotrexate in monotherapy and combination therapy in patients with rheumatoid arthritis

Arthritis Research & Therapy ◽

10.1186/s13075-017-1468-9 ◽

2017 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Sytske Anne Bergstra ◽

Cornelia F. Allaart ◽

Rosaline van den Berg ◽

Arvind Chopra ◽

Nimmisha Govind ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Combination Therapy ◽

Clinical Response ◽

Low Dose ◽

High Dose ◽

Short Term ◽

Dose Methotrexate

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Low-Dose Methotrexate Use in Idiopathic Granulomatous Mastitis: An Alternative Treatment Method

Breast Care ◽

10.1159/000513879 ◽

2021 ◽

pp. 1-6

Author(s):

Mehmet Tolga Kafadar ◽

Mehmet Veysi Bahadır ◽

Sadullah Girgin

Keyword(s):

Side Effects ◽

Alternative Treatment ◽

Low Dose ◽

Treatment Method ◽

Treatment Modalities ◽

Unknown Etiology ◽

Partial Recovery ◽

Granulomatous Mastitis ◽

Idiopathic Granulomatous Mastitis ◽

Dose Methotrexate

Background: Idiopathic granulomatous mastitis (IGM) is a rare, recurrent and progressive breast disease with an unknown etiology. Patients with IGM will probably face stressful, time-consuming treatment procedures with side effects due to medications. There are different treatment modalities in clinical use including medical and surgical interventions. Objective: The aim of this study was to present the results of using the combination therapy of low-dose methotrexate (MTX) and steroid in IGM. Methods: Seventeen patients diagnosed with IGM and treated with MTX were included into the study. Low-dose MTX at 5 mg/week and 8 mg/day prednisone were given for 2–3 months. Results: After 2–3 months of treatment, 10 patients exhibited (58.5%) complete, 3 patients (17.6%) partial recovery, and no response to the treatment process was observed in 4 patients (23.5%). No side effects of MTX and recurrent events were noted in any of the patients. Conclusion: Low-dose MTX and prednisone treatment for IGM patients, who did not respond to steroids alone, should be considered as an alternative treatment method instead of surgical intervention.

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Efficacy, Safety and Steroid-sparing Effect of Topical Cyclosporine A 0.05% for Vernal Keratoconjunctivitis in Indian Children

Journal of Ophthalmic and Vision Research ◽

10.18502/jovr.v14i4.5439 ◽

2019 ◽

Cited By ~ 1

Author(s):

Arkendu Chatterjee ◽

Sabyasachi Bandyopadhyay ◽

Samir Kumar Bandyopadhyay

Keyword(s):

Placebo Group ◽

Side Effects ◽

Cyclosporine A ◽

Controlled Study ◽

Vernal Keratoconjunctivitis ◽

Indian Children ◽

Steroid Dependent ◽

Sparing Effect ◽

Steroid Sparing

Purpose: To evaluate the efficacy, safety, and steroid-sparing effect of topical cyclosporine A (Cs A) 0.05% in patients with moderate to severe steroid dependent vernal keratoconjunctivitis (VKC). Methods: A prospective, comparative, placebo controlled study was carried out on 68 VKC patients, with 34 patients treated with topical Cs A 0.05% and the remaining 34 with topical carboxymethyl cellulose 0.5% (placebo). Both groups also received topical loteprednol etabonate 0.5%. Symptom (itching, photophobia, tearing, and discharge) score, sign (tarsal and limbal papillae, corneal involvement, and conjunctival hyperemia) score, and drug score (steroid drop usage/day/eye) were recorded at baseline and each followup visit. The intraocular pressure (IOP) measurement and evaluation of any ocular side effects were carried out. Results: Significant reduction in symptom score and sign score was seen in both groups. Cs A group significantly showed more reduction in symptom (P < 0.0001 in all follow-up visits) and sign (P < 0.0001 in all follow-up visits) scores compared to the placebo group. At day 7, mean steroid usage reduced from 4 to 3.44 ± 0.5 and 3.79 ± 0.4 in Cs A and placebo groups, respectively (P < 0.0001). Steroid drops completely stopped in 21 patients at day 60 in the Cs A group compared to none in the placebo group. No significant rise in IOP or any side effects were noted in either group. Conclusion: Topical Cs A 0.05% is effective and safe in patients with moderate to severe VKC with good steroid-sparing effect.

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Clinical characteristics and risk factors for low dose methotrexate toxicity: A cohort of 28 patients

Autoimmunity Reviews ◽

10.1016/j.autrev.2014.08.027 ◽

2014 ◽

Vol 13 (11) ◽

pp. 1109-1113 ◽

Cited By ~ 61

Author(s):

Shaye Kivity ◽

Yaron Zafrir ◽

Ronen Loebstein ◽

Rachel Pauzner ◽

Meir Mouallem ◽

...

Keyword(s):

Risk Factors ◽

Clinical Characteristics ◽

Low Dose ◽

Dose Methotrexate ◽

Methotrexate Toxicity

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Combination Treatment of Essential Thrombocythemia with Hydroxyurea and Anagrelide

Blood ◽

10.1182/blood.v118.21.5177.5177 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5177-5177

Author(s):

Inhye E. Ahn ◽

Ethan A. Natelson ◽

Lawrence Rice

Keyword(s):

Side Effects ◽

Combination Therapy ◽

Essential Thrombocythemia ◽

Combination Treatment ◽

Low Dose ◽

Conflicts Of Interest ◽

Combination Regimen ◽

Bleeding Events ◽

Jak2 Mutation ◽

Platelet Counts

Abstract 5177 BACKGROUND: Hydroxyurea and anagrelide are therapeutic options for essential thrombocythemia (ET) with distinct mechanism of actions and side effect profiles. However, therapeutic goals may not be achieveable due to drug intolerance or disease resistance. Here we report our successful clinical experience with combination treatment with hydroxyurea and anagrelide. METHODS: Medical records of six patients who were on the combination treatment for the ET were retrospectively reviewed. All had history of unsuccessful monotherapy with either hydroxyurea or anagrelide. RESULTS: All patients were female with median age of 59.5 years. All were positive for the V617_ jak2 mutation. Two had prior major thromboses (portal vein; ischemic stroke), and one had Raynaud's disease. Reasons for failure of hydroxyurea monotherapy were leukopenia and/or inadequate platelet reduction, while reasons for anagrelide failure were palpitations and orthostasis. Rather than discontinue the primary drug, doses were lowered to a tolerable level and the second agent was added. These patients have been treated with the combination of hydroxyurea and anagrelide for a mean duration of 4.89+ years. Combination regimen achieved 64% reduction of platelet counts (mean best platelet counts during treatment 328×109/L), while maintaining adequate leukocyte counts (range 3.64–7.88 × 109/L). Relatively low daily doses of hydroxyurea (mean 684mg/day) and anagrelide (1.7mg/day) were required. Adverse events noted during the combination therapy were one case with rectal bleeding and two cases of myelofibrosis. One patient returned to monotherapy due to persistent headache to low-dose anagrelide. No arterial or venous thromboses bleeding events have occurred. CONCLUSION: This is the longest follow-up experience of hydroxyurea and anagrelide combination therapy in ET that has been resistant to monotherapy or where high monotherapy doses could not be tolerated. The low-dose combination regimen was able to achieve clinical and laboratory response in all patients with a low incidence of medication side effects. This strategy is made more attractive by data that hydroxyurea may be more effective in prevent arterial events while anagrelide was found more effective in preventing venous clots, but conclusions on superior efficacy of the combination would require formal study. We recommend that rather than substitute for an agent that has had partial success or is causing dose-related side-effects, the dose can be adjusted and a second agent added. Disclosures: No relevant conflicts of interest to declare.

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