How I Treat ITP: From Steroids to Newer Therapies

Treating immune thrombocytopenia begins with corticosteroids for nearly every newly diagnosed adult, but the treatment landscape has expanded dramatically over the past two decades, giving clinicians and patients far more options when steroids fall short. ITP is driven by an immune system that both destroys circulating platelets and hampers the bone marrow’s ability to produce new ones, which means effective treatment often needs to address more than one problem at once. The path from diagnosis to a durable response can involve several lines of therapy, and understanding what each option does and when it fits best makes a real difference in outcomes.

Why Platelets Drop in ITP

ITP is not a single clean mechanism. The immune system attacks platelets through at least two routes: antibodies that tag platelets for destruction, and T cells that directly kill them or suppress new platelet production in the bone marrow.¹ The bone marrow itself is also affected. Megakaryocytes, the large cells that bud off platelets, are often impaired or insufficiently stimulated, so the marrow cannot compensate for the accelerated peripheral destruction.² This dual problem explains why some patients respond beautifully to one therapy and not at all to another: a drug that curbs antibody-mediated destruction may do nothing for someone whose disease is primarily T-cell-driven. It also explains the rationale behind the expanding toolkit of treatments.

First-Line Therapy With Corticosteroids

Corticosteroids remain the standard opening move. The two most common regimens are daily prednisone tapered over several weeks and short pulses of high-dose dexamethasone. Both work by broadly dampening the immune response, reducing the antibody and cellular attack on platelets. The practical question is which steroid to choose and what to expect.

High-dose dexamethasone tends to produce faster and higher initial response rates. A multicenter randomized trial found that one or two courses of dexamethasone achieved an overall initial response in about 82% of patients compared with roughly 67% on prednisone, and complete responses were nearly double.³ A separate randomized trial confirmed this pattern, showing initial responses of about 94% with dexamethasone versus 79% with prednisone. But prednisone pulled ahead at the 12-month mark: roughly 81% of prednisone responders maintained their response compared with about 56% of dexamethasone responders.⁴

A systematic review and meta-analysis that pooled the available trials found no meaningful difference in overall platelet response at six months, with response rates of roughly 54% for dexamethasone and 43% for prednisone. Dexamethasone did have fewer reported side effects.⁵ The bottom line: dexamethasone gets platelets up faster, but sustaining that response is a coin flip either way. Neither steroid reliably cures ITP, and prolonged steroid courses carry well-known consequences including weight gain, mood changes, high blood sugar, and bone thinning. Most hematologists aim to taper steroids as quickly as possible and pivot to a second-line agent if remission does not stick.

Intravenous Immunoglobulin for Rapid Rescue

When you need a quick platelet bump, intravenous immunoglobulin (IVIg) delivers. It raises platelet counts in over 80% of patients, often within days, but the effect is temporary: platelets typically drift back down within about four weeks.⁶ This makes IVIg ideal for buying time before surgery, stopping active bleeding, or bridging to a slower-acting therapy. It is not a long-term solution by itself.

Rituximab as a Second-Line Option

Rituximab depletes B cells, the immune cells that produce the antiplatelet antibodies driving much of the destruction. Its initial overall response rate hovers around 57% in both adults and children. The catch is durability. At five years, only about 21% of adults and 26% of children who initially responded maintained a treatment-free response.⁷ Children who made it past two years without relapsing tended to stay in remission, whereas adults continued to relapse beyond that window.⁸

An interesting finding from studying rituximab responders is that the benefit goes beyond just removing antibodies. Patients who achieved a durable response showed normalization of their T-cell abnormalities, including shifts in T-helper cell ratios and reduced expression of cell-death signals that were elevated before treatment. Nonresponders showed no such correction.⁹ This suggests rituximab works best when the disease is tightly linked to antibody-driven immune dysregulation and less well when T-cell mechanisms dominate independently.

The Declining but Still Relevant Role of Splenectomy

The spleen is the primary site where antibody-coated platelets get filtered out and destroyed, so removing it has long been one of the most effective treatments for ITP. Response rates after splenectomy are high, but the procedure carries permanent risks: lifelong increased vulnerability to certain bacterial infections and a higher rate of cardiovascular complications. With the arrival of rituximab and thrombopoietin receptor agonists, splenectomy has been pushed further down the treatment ladder. Most specialists now try to avoid it within the first 12 months after diagnosis to allow time for spontaneous or drug-induced remissions, and it is approached with particular caution in older adults, who have greater surgical risk and lower response rates, and in young children.¹⁰ Splenectomy is not obsolete, but it is increasingly a last resort rather than an early second-line move.

Thrombopoietin Receptor Agonists

Rather than suppressing the immune attack, thrombopoietin receptor agonists (TPO-RAs) take a completely different approach: they stimulate the bone marrow to produce more platelets, outpacing the rate of destruction. The licensed options include romiplostim (a weekly injection), eltrombopag (a daily oral tablet), and the newer avatrombopag (also oral). A meta-analysis covering both adults and children found that TPO-RAs produced longer durations of platelet response, higher overall response rates, less need for rescue therapy, and fewer bleeding events compared with placebo, without a higher rate of adverse events.¹¹

The practical differences between individual TPO-RAs matter more than you might expect. Eltrombopag requires a four-hour food-restricted window because dietary calcium and other minerals interfere with its absorption. Avatrombopag has no such restriction and can be taken with meals, which reduces variability in blood levels.¹² Avatrombopag also shows consistent drug exposure across different ethnic populations and has not been linked to the liver toxicity seen in some eltrombopag patients.¹³ In some ITP patients, avatrombopag can even be dosed less frequently than once daily, which adds convenience. Network meta-analysis data suggest avatrombopag may edge out eltrombopag in overall platelet response rates, though all three agents are considered effective.¹¹

TPO-RAs do not cure ITP. Most patients see their platelet counts drop again once the drug is stopped. In that sense, they are long-term maintenance therapy for many people. But for those who cannot tolerate steroids or rituximab, or who want to avoid splenectomy, they represent a well-tolerated way to keep platelets in a safe range.

Fostamatinib and a Different Mechanism

Fostamatinib targets a protein called spleen tyrosine kinase (SYK) that sits at the center of the pathway macrophages use to engulf antibody-coated platelets. By blocking SYK, fostamatinib slows that phagocytic destruction. It was the first oral SYK inhibitor approved for adults with chronic ITP who had failed at least one prior therapy.¹⁴ A meta-analysis of randomized controlled trials found that fostamatinib was significantly better than placebo at achieving stable platelet responses by 24 weeks, including in patients who started with very low platelet counts below 15,000 per microliter.¹⁵ Its niche is the heavily pretreated patient who has already cycled through corticosteroids, TPO-RAs, rituximab, or splenectomy without lasting success.

Emerging Therapies on the Horizon

The newest wave of ITP treatments targets the disease at fundamentally different immunological checkpoints.

Efgartigimod is an engineered antibody fragment that blocks the neonatal Fc receptor (FcRn), a molecule that normally rescues IgG antibodies from degradation and recycles them back into circulation. By blocking FcRn, efgartigimod accelerates the breakdown of all IgG, including the autoantibodies that drive platelet destruction.¹⁶ In a Phase 2 trial, four weekly infusions of efgartigimod reduced total IgG levels by up to roughly 64% from baseline. Among patients receiving the drug, 46% reached a platelet count of at least 50,000 on two or more occasions, compared with 25% on placebo, and 38% maintained that level for at least 10 cumulative days versus 0% on placebo.¹⁷ A Phase 3 trial has since been completed, and the approach remains a promising alternative for patients whose disease is clearly antibody-mediated.¹⁸

Rilzabrutinib is an oral Bruton’s tyrosine kinase (BTK) inhibitor that works through a dual mechanism: it reduces macrophage-mediated platelet destruction and cuts back the production of pathogenic autoantibodies.¹⁹ Unlike earlier BTK inhibitors used in blood cancers, rilzabrutinib binds its target reversibly, which is thought to improve its safety profile. Clinical trials are ongoing.

Sutimlimab takes yet another angle by blocking C1s, a component of the classical complement pathway. Complement-mediated destruction may be an underappreciated contributor to platelet loss in some ITP patients, and early-phase data are exploring whether selectively shutting down this pathway helps those with refractory disease who have already failed multiple other treatments.²⁰

Managing a Crisis Bleed

When someone with ITP develops life-threatening bleeding, the treatment approach changes from sequential therapy to throwing everything at the problem simultaneously. An international guideline on emergency management of critical ITP bleeding recommends the combined use of high-dose corticosteroids, high-dose IVIg, platelet transfusions, the antifibrinolytic drug tranexamic acid, and a TPO-RA, all started together.²¹ Platelet transfusions in ITP are normally avoided because the transfused platelets are destroyed just as fast as the patient’s own, but in a life-threatening bleed the brief bump can be lifesaving while the other agents take effect.

ITP in Children and During Pregnancy

Childhood ITP is a different beast from the adult form. Most children recover spontaneously within weeks to months, and guidelines support careful observation rather than automatic treatment when bleeding is mild. Despite this, a multicenter study found that a large proportion of hospitalized children without significant bleeding were still receiving drug therapy, suggesting overtreatment remains common.²² A randomized trial comparing IVIg with observation alone in newly diagnosed children with platelet counts at or below 20,000 found that IVIg produced faster responses but did not significantly reduce the rate of chronic ITP at 12 months (10% with IVIg versus 12% with observation). Severe bleeding was rarer in the IVIg group (1% versus 9%), which supports using it when the bleeding risk is high.²³

ITP during pregnancy presents unique challenges. Diagnosis is complicated because several pregnancy-specific conditions can mimic or overlap with ITP, and there is no confirmatory test. Treatment options are largely limited to corticosteroids and IVIg, since most newer agents have not been studied in pregnant women.²⁴ The treatment goal during pregnancy is pragmatic: keep platelets above 30,000 during gestation and above 50,000 for delivery, rather than chasing normal counts.²⁵ Since maternal antibodies can cross the placenta and affect fetal platelets, any treatment decision must weigh risks to the baby as well.

The Helicobacter pylori Connection

One of the more surprising findings in ITP management is that a stomach bacterium can cause it. A systematic review of 25 studies including over 1,500 patients found that among those who had H. pylori infection eradicated, roughly 43% achieved a complete response and about 50% had an overall response, with platelet counts rising substantially.²⁶ In patients whose infection was successfully cleared, platelet counts one year later were roughly two to three times their baseline levels, while those with persistent infection showed only modest improvement.²⁷ Most responders remain in lasting remission with no relapse for many years, suggesting a genuine cure rather than suppression.²⁸ Testing for H. pylori is cheap and the treatment is a short course of antibiotics, making this one of the highest-value steps in the early workup of any adult with ITP.

Predicting Who Will Respond to What

One of the most frustrating aspects of ITP management is the trial-and-error nature of therapy selection. Research is working to change that. A study analyzing biomarkers for steroid response identified six factors that predicted a poor response to corticosteroids, including advanced age (over 80), very low starting platelet counts, and high levels of platelet-associated antibodies.²⁹ A more ambitious effort built separate predictive scoring models for three different treatment classes: corticosteroids, TPO-RAs, and rituximab. Each model used a different set of immune markers and clinical variables to estimate the likelihood of response.³⁰ Proteomic analysis has identified additional plasma proteins that differ between treatment responders and nonresponders, though these findings await validation in larger groups.³¹ None of these tools are ready for routine clinical use yet, but they point toward a future where blood tests at diagnosis could guide the first treatment choice rather than defaulting everyone to the same steroid regimen.

What These Therapies Actually Cost

Access to newer ITP therapies is shaped as much by economics as by efficacy. A cost-utility analysis of TPO-RAs in children who failed first-line therapy estimated an incremental cost of about $27,000 more than non-TPO-RA approaches over two years, with modest quality-of-life gains. The resulting cost-effectiveness ratio put TPO-RAs above the conventional willingness-to-pay threshold of $100,000 per quality-adjusted life-year, though the picture improved substantially when projected over five years.³² Among the TPO-RAs themselves, head-to-head economic comparisons vary by country: a UK analysis found avatrombopag dominated romiplostim (more effective and less expensive) while being cost-effective compared to eltrombopag at a very low incremental cost per quality-adjusted life-year.³³ In China, a similar analysis favored hetrombopag (a locally available agent) as the lowest-cost strategy, though avatrombopag yielded the highest quality-of-life gains.³⁴ The takeaway is that which TPO-RA makes the most economic sense depends heavily on local drug pricing and healthcare system structure, and the “best” agent in one country may not be the most accessible or affordable in another.