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Combination therapy of interferon Beta-1b and tacrolimus: a pilot safety study.

ABSTRACT: Tacrolimus is a calcineurin inhibitor which works to induce immune suppression by preventing cytokine transcription and lymphocyte activation. Combining the immunomodulator interferon beta-1b (Betaseron) with the immunosuppressant tacrolimus (Prograf) may have the potential of additive therapeutic benefit through the complementary mechanisms of action of these two therapeutics. In this randomized, open-label, multicenter, two-arm pilot study, the authors examined the safety and tolerability of the combination of interferon beta-1b and tacrolimus in relapsing remitting (RRMS) and secondary progressive (SPMS) multiple sclerosis patients who have failed one or more immunomodulatory therapies. Patients (n = 25) received a combination of interferon beta-1b subcutaneously every other day and oral tacrolimus (low blood level tacrolimus, 1-5?ng/mL, or high blood level tacrolimus, 5-10?ng/mL) for a period of 38 weeks. The combination therapy of interferon beta-1b and tacrolimus over the 10-month period of the study was shown to be safe and relatively well tolerated. There were no unexpected adverse events occurring as the result of the combination therapy. Further study of this combination therapy in patients with multiple sclerosis unresponsive to conventional therapy is warranted.

SUBMITTER: Jacques F

PROVIDER: S-EPMC3431088 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Combination therapy of interferon Beta-1b and tacrolimus: a pilot safety study.

Jacques F F Gaboury I I Christie S S Grand'maison F F

Multiple sclerosis international 20120815

Tacrolimus is a calcineurin inhibitor which works to induce immune suppression by preventing cytokine transcription and lymphocyte activation. Combining the immunomodulator interferon beta-1b (Betaseron) with the immunosuppressant tacrolimus (Prograf) may have the potential of additive therapeutic benefit through the complementary mechanisms of action of these two therapeutics. In this randomized, open-label, multicenter, two-arm pilot study, the authors examined the safety and tolerability of t ...[more]

PMID: 22966460

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Project description:Introduction: To compare a schedule with cyclic withdrawal (CW) of interferon beta (IFN-b) 1b, respect to the full regimen (FR), in relapsing-remitting MS (RR-MS). Methods: Participants were randomly assigned to CW or FR schedule and monthly monitored with brain MRI scans for 12 months (three of run-in and 9 of treatment). CW schedule included drug withdrawal for 1 month after two of treatment for a total of three quarters over the 9-month treatment period. The assessing neurologist and the expert neuroradiologists were blind. After the blind phase of the study all participants took their indicated disease modifying therapies in a prospectively planned, open-label extension phase (up to 120 months). Results: Of 60 randomized subjects 56 (29 in FR and 27 in CW group) completed the single-blind phase: the two groups were comparable, except for a non-significant difference in the number of contrast-enhanced lesions (CEL) at the end of run-in. The two-sided 90% CI for the ratio between median number of cumulative CEL was 0.29-1.07, allowing to significantly reject the null hypothesis of a ratio ≥1.2 and to meet the primary end-point of non-inferiority (the threshold and the ratio between median were chosen according to the non-normal distribution of the data). The differences (CW vs. FR) were also non-significant for secondary end points: mean cumulative number of T2-weighted new and enlarging lesions (3.48 ± 5.34 vs. 3.86 ± 6.76); mean number and volume (cm3) of black holes (1.24 ± 1.61 vs. 2.71 ± 4.56; 489.11 ± 1488.12 vs. 204.48 ± 396.98); number of patients with at least an active scan (21 vs. 22); mean relapse rate (0.52 ± 0.89 vs. 0.34 ± 0.66), relapse risk ratio adjusted for baseline variables (2.15 [0.64-7.18]), EDSS score (1.0 [1-1.56] vs. 1.5 [1-1.78]), proportion of patients with antibodies anti-IFN (5 [21%] vs. 8 [36%]). Fifty-four patients (27 for each study arm) completed the open-label phase. The annualized RR, EDSS, proportion of patients shifting to progressive disease and hazard ratio of shifting, adjusting for baseline covariates, were comparable between the two study groups. Conclusions: A calendar with CW was non-inferior than FR at the beginning of IFN-b therapy, and may not affect the long-term outcome. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT00270816.

Project description:The only treatment currently available for patients with severe infantile osteopetrosis is hematopoietic cell transplantation (HCT). HCT-related toxicity and mortality risks typically preclude its use in non-infantile patients, and other therapies are needed for these patients who have significant disease-related morbidity. Interferon gamma-1b is currently approved by the U.S. Food and Drug Administration (FDA) for treatment of severe infantile osteopetrosis (autosomal recessive osteopetrosis [ARO]). However, little is known about the effects of interferon gamma-1b in non-infantile osteopetrosis. Thus, this pilot study aimed at testing the safety and tolerability of interferon gamma-1b in patients with non-infantile osteopetrosis and assessing the clinical effects. We performed a 12-month, open-label, multi-center pilot study involving patients >1 year-old diagnosed radiographically with osteopetrosis. Patients were initiated on interferon gamma-1b subcutaneously 15 μg/m2 three times weekly, to be titrated over 3 weeks to a goal of 100 μg/m2 three times weekly. The primary aim was safety and tolerability. The secondary aims were to assess changes in peripheral quantitative computed tomography (pQCT), dual-energy x-ray absorptiometry (DXA) bone mineral density (BMD) Z-scores, bone biomarkers, and quality-of-life (QOL) measures. Four of the five participants enrolled withdrew from the study between 3 and 9 months due to intolerability of interferon gamma-1b-related flu-like symptoms. The last participant completed the study with the addition of prednisone on days of interferon gamma-1b administration. DXA and pQCT outcomes were stable over 6-12 months, and there were no clear trends in bone biomarkers or QOL measures. No serious drug-related adverse events were reported during this study. Interferon gamma-1b was only tolerable in one of five participants with the addition of prednisone. The stabilization of BMD and other measures of bone health during this study suggest possible positive effects of interferon gamma-1b on osteopetrosis; however, additional data are needed before conclusions on treatment efficacy can be made. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Project description:BackgroundAccurate measurement of medication adherence using classical observational studies typically depends on patient self-reporting and is often costly and slow. In contrast, digital observational studies that collect data directly from the patient may pose minimal burden to patients while facilitating accurate, timely, and cost-efficient collection of real-world data. In Germany, ~80% of patients with multiple sclerosis (MS) treated with interferon beta 1b (Betaferon) use an electronic autoinjector (BETACONNECT), which automatically records every injection. Patients may also choose to use a medical app (myBETAapp) to document injection data and their well-being (using a "wellness tracker" feature).ObjectiveThe goal of this pilot study was to establish a digital study process that allows the collection of medication usage data and to assess medication usage among patients with MS treated with interferon beta-1b who use myBETAapp.MethodsThe PROmyBETAapp digital observational study was a mixed prospective and retrospective, noninterventional, cohort study conducted among users of myBETAapp in Germany (as of December 2017: registered accounts N=1334; actively used accounts N=522). Between September and December 2017, users received two invitations on their app asking them to participate. Interested patients were provided detailed information and completed an electronic consent process. Data from consenting patients' devices were collected retrospectively starting from the first day of usage if historical data were available in the database and collected prospectively following consent attainment. In total, 6 months of data on medication usage behavior were collected along with 3 months of wellness tracker data. Descriptive statistics were used to analyze persistence, compliance, and adherence to therapy.ResultsOf the 1334 registered accounts, 96 patients (7.2%) provided informed consent to participate in the study. Of these, one patient withdrew consent later. For another patient, injection data could not be recorded during the study period. Follow-up of the remaining 94 patients ended in May 2018. The mean age of participants was 46.6 years, and 50 (53%) were female. Over the 6-month study period, persistence with myBETAapp usage was 96% (90/94), mean compliance was 94% of injections completed, and adherence (persistence and ≥80% compliance) was 89% (84/94). There was no apparent difference between male and female participants and no trend across age groups. The wellness tracker was used by 21% of participants (20/94), with a mean of 3.1 entries per user.ConclusionsThis study provides important information on medication usage among patients with MS treated with interferon beta-1b and on consenting behavior of patients in digital studies. In future studies, this approach may allow patients' feedback to be rapidly implemented in existing digital solutions.Trial registrationClinicalTrials.gov NCT03134573; https://clinicaltrials.gov/ct2/show/NCT03134573.

Dataset Information

Combination therapy of interferon Beta-1b and tacrolimus: a pilot safety study.

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Combination therapy of interferon Beta-1b and tacrolimus: a pilot safety study.

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