--- title: Promising Monoclonal Antibody Offers New Steroid-Sparing Hope for IgG4-RD description: Results from the Phase 3 MITIGATE trial of inebilizumab have raised hopes of a steroid-sparing treatment for IgG4-RD. image: https://www.steritas.com/hubfs/Insights%20images%202024%20onwards/ST0149%20MITIGATE%20trial/Steritas_ST0149_MITIGATE_Trial_DEC_2024_Blog_Image_1080x1080pxl_070824_VF.jpg --- [News](https://www.steritas.com/news) ## Promising Monoclonal Antibody Offers New Steroid-Sparing Hope for IgG4-RD January 14 2025 Results from the Phase 3 MITIGATE trial of a biologic called inebilizumab have raised hopes the tide may be turning in the hunt for an alternative treatment to steroids for IgG4-related disease (IgG4-RD).[1] IgG4-RD is a rare, autoimmune inflammatory condition affecting an estimated 40,000 patients in the US and hundreds of thousands worldwide.[2]  Currently, there are no approved treatments for IgG4-RD, and nearly all patients receive glucocorticoids as the standard first-line treatment. The results from the MITIGATE trial showed that patients treated with inebilizumab, a humanized monoclonal antibody that targets CD19, achieved promising remission rates.[1]    IgG4-RD can affect any organ in the body and is characterized by the development of lesions rich in CD19+ B cells, which are thought to drive fibrosis and inflammation.[1] IgG4-RD responds well to steroid treatment, making it the mainstay approach for the condition. However, while steroids are very effective in treating IgG4-related disease, the long list of toxicities associated with their use makes them dangerous in the long term, and immunosuppressive therapies, such as rituximab, often supplement their use.   Rituximab, a CD20-targeted B cell-depleting agent, was demonstrated to have some efficacy against IgG4-RD in open-label studies,[3] but has yet to be tested in a randomized clinical trial for IgG4-RD. It is thought that CD19-targeting therapies such as inebilizumab and [obexelimab](https://www.steritas.com/insights/obexelimab-a-new-hope-for-igg4-rd-treatment) (another treatment currently in clinical trials for IgG4-RD) may be more effective treatments for the disease because they target a larger subset of B cells compared to agents that target CD20.[1] One of the co-authors of the trial was Wen Zhang, MD PhD, [who recently told Steritas](https://www.steritas.com/insights/in-conversation-with-wen-zhang-md-phd):   *“Steroid treatment really is a double-edged sword. While steroids have a dramatic effect on inflammatory diseases such as IgG4-related disease, there is a long list of toxicities associated with their use… and whenever my patients suffer any of these, I really feel sorry for them and wish we had alternative treatments we could prescribe.”  *   #### Inebilizumab remission rates are almost 5x those of placebo The MITIGATE Phase 3 double-blind, randomized placebo-controlled trial was conducted at 80 sites across 22 countries. One hundred thirty-five adult patients, with a new or existing diagnosis, were randomized 50:50 to receive either inebilizumab or placebo. All participants had an IgG4-related disease flare, which required initiation or continuation of glucocorticoid treatment for 3 to 8 weeks prior to randomization.     Steroid doses were reduced to 20mg a day before randomization and then tapered to zero over the first 8 weeks of the study. Steroid therapy was allowed to treat flares but not to prevent them. Overall, 127 (94.1%) participants completed the 52-week treatment period, with the results offering real hope of a new and effective steroid-sparing therapy for IgG4-RD: - Inebilizumab reduced the risk of treated IgG4-related disease flares by 87% - 57% of inebilizumab participants had flare-free, treatment-free complete remissions over the 52 weeks compared with 22% for the placebo arm - The total steroid dose per participant was more than ten times higher in the placebo group - 118.3mg in the inebilizumab group - 1384.5mg in the placebo group   From a safety perspective, the number of participants with at least one adverse event was similar in the two arms. Adverse events of grade 3 and above were higher in the inebilizumab arm (18%) than in the placebo arm (12%). Infection rates were also higher in the inebilizumab arm, including COVID-19 (24%) and urinary tract infections (12%). The MITIGATE study has established the efficacy of CD19-targeted B cell depletion in IgG4-RD, but longer follow-up is required to establish the long-term safety and efficacy of this approach. #### Could the GTI support the stratified use of expensive new therapies? While the IgG4-RD world awaits the results of the longer-term study into inebilizumab, there is still much we can learn from the MITIGATE study. The high proportion of inebilizumab patients who achieved steroid-free remission and a total steroid dose of less than 10% of that in the placebo arm suggest real potential as a steroid-sparing option for IgG4-RD.   With the promise of new, monoclonal antibody therapies for IgG4-related disease on the horizon, it’s worth exploring the challenge of ensuring access for those patients who would benefit most from the treatment. Monoclonal antibodies have become a powerful tool in modern medicine, but they’re expensive drugs; the average price for monoclonal antibody treatment in the United States is $15k-200k per year. As a result, access to these drugs can be limited, particularly in low- and middle-income countries.[4]  A recent study published in the Journal of Rheumatology demonstrated the Steritas GTI could be used in a clinical practice setting to prospectively assess glucocorticoid-related toxicity in patients. The study showed the GTI is sensitive enough to identify patient-specific sensitivity to steroid-toxicity and has the potential to be used to identify patients with the highest steroid-toxicity burden and prioritize their access to these new therapies.   ### From Boston to Beijing. IgG4-RD and Steroid-toxicity #### Access our on-demand webinar on IgG4-RD [![Access webinar](https://no-cache.hubspot.com/cta/default/8277484/5322996a-d97d-435b-850d-e192a48db38f.png)](https://cta-redirect.hubspot.com/cta/redirect/8277484/5322996a-d97d-435b-850d-e192a48db38f)   #### References 1. Stone JH, Khosroshahi A, Zhang W et al. Inebilizumab for treatment of IgG4-Related Disease.  NEJM 2024. Published 14th November online ahead of print. [DOI: 10.1056/NEJMoa2409712](https://doi.org/10.1056/NEJMoa2409712) 2. IgG4ward. [https://igg4ward.org/about-igg4ward/](https://igg4ward.org/about-igg4ward/) accessed December 9th, 2024 3. Caruthers MN, Topazian MD, Khosroshahi A et. al. Rituximab for IgG4-related disease: a prospective, open-label trial.  Ann. Rheum. Dis. 74:1171-1177 (2015) [DOI: 10.1136/annrheumdis-2014-206605](https://doi.org/10.1136/annrheumdis-2014-206605) 4. Expanding access to monoclonal anti-body-based products: a global call to action [https://wellcome.org/reports/expanding-access-monoclonal-antibodies](https://wellcome.org/reports/expanding-access-monoclonal-antibodies), accessed December 9th, 2024 --- ###### Categories: [IgG4-RD](https://www.steritas.com/insights/tag/igg4-rd) [mailto:?subject=Check%20out%20https://www.steritas.com/insights/promising-monoclonal-antibody-offers-new-steroid-sparing-hope-for-igg4-rd&utm_medium=social&utm_source=email%20&body=Check%20out%20https://www.steritas.com/insights/promising-monoclonal-antibody-offers-new-steroid-sparing-hope-for-igg4-rd&utm_medium=social&utm_source=email](mailto:?subject=Check%20out%20https://www.steritas.com/insights/promising-monoclonal-antibody-offers-new-steroid-sparing-hope-for-igg4-rd&utm_medium=social&utm_source=email%20&body=Check%20out%20https://www.steritas.com/insights/promising-monoclonal-antibody-offers-new-steroid-sparing-hope-for-igg4-rd&utm_medium=social&utm_source=email) ```json { "@context" : "https://schema.org", "@type" : "BlogPosting", "author" : { "@type" : "Person", "name" : "Steritas", "url" : "https://www.steritas.com/insights/author/steritas" }, "dateModified" : "2025-01-14T09:15:00.757Z", "datePublished" : "2025-01-14T09:15:00.000Z", "headline" : "Promising Monoclonal Antibody Offers New Steroid-Sparing Hope for IgG4-RD", "image" : [ "https://www.steritas.com/hubfs/Insights%20images%202024%20onwards/ST0149%20MITIGATE%20trial/Steritas_ST0149_MITIGATE_Trial_DEC_2024_Blog_Image_1080x1080pxl_070824_VF.jpg" ], "mainEntityOfPage" : { "@id" : "https://www.steritas.com/insights/promising-monoclonal-antibody-offers-new-steroid-sparing-hope-for-igg4-rd", "@type" : "WebPage" }, "publisher" : { "@type" : "Organization", "logo" : { "@type" : "ImageObject", "url" : "https://www.steritas.com/hubfs/Screen%20Shot%202022-07-13%20at%2011.33.19%20AM.png" }, "name" : "Steritas LLC" } } ```