The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency meets monthly to evaluate safety signals for medicinal products and recommend appropriate regulatory actions. At its meeting of 9–12 February 2026, PRAC adopted important recommendations concerning three distinct medicinal products: the live attenuated chikungunya vaccine, omalizumab, and risankizumab.
The signals include a new aspect of a known risk (aseptic meningitis with chikungunya vaccine), a rare but serious adverse event (acquired haemophilia with omalizumab), and a routine pharmacovigilance recommendation (pemphigoid with risankizumab).
1. Introduction: The Role of PRAC in Medication Safety
The Pharmacovigilance Risk Assessment Committee (PRAC) is the European Medicines Agency’s committee responsible for assessing and monitoring safety issues for human medicines. Composed of experts from EU Member States, PRAC plays a critical role in:
- Detecting and evaluating safety signals
- Assessing risk management plans
- Evaluating periodic safety update reports
- Making recommendations for product information updates
- Requesting supplementary information from marketing authorisation holders (MAHs)
At its meeting of 9–12 February 2026, PRAC adopted recommendations for three safety signals, requiring varying levels of action from MAHs—from routine pharmacovigilance to submission of supplementary information and assessment in upcoming Periodic Safety Update Reports (PSURs) .
2. Signal 1: Chikungunya Vaccine (Live) – Aseptic Meningitis
2.1 Background: Chikungunya Virus and Vaccine
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes. The disease is characterized by acute febrile illness with severe, often debilitating polyarthralgia. Prior to 2024, no specific treatment or vaccine was available for chikungunya .
In November 2023, the U.S. Food and Drug Administration approved Ixchiq, the first chikungunya vaccine, developed by Valneva Austria GmbH. This was followed by European Commission marketing authorisation in June 2024 for individuals aged 18 years and older .
2.2 The Signal: Aseptic Meningitis
PRAC identified a new aspect of the known risk of aseptic meningitis associated with the live attenuated chikungunya vaccine .
2.2.1 What is Aseptic Meningitis?
Aseptic meningitis is an inflammation of the meninges (the protective membranes covering the brain and spinal cord) not caused by bacterial infection. It is typically viral in origin but can also result from medications, vaccines, or other non-infectious causes.
| Feature | Description |
|---|---|
| Definition | Meningeal inflammation with negative bacterial cultures and no evidence of bacterial pathogens in cerebrospinal fluid (CSF) |
| Common Causes | Viruses (enteroviruses, herpes simplex, HIV), medications (NSAIDs, antibiotics, IVIG), vaccines (rare), autoimmune conditions |
| Pathophysiology | Inflammatory response in the subarachnoid space; may be directly viral (vaccine-strain virus) or immune-mediated |
| Clinical Presentation | Headache, fever, neck stiffness, photophobia, nausea, vomiting |
| Diagnosis | Lumbar puncture: lymphocytic pleocytosis, elevated protein, normal glucose; negative bacterial cultures; PCR for vaccine-strain virus may be considered |
| Prognosis | Generally self-limited with supportive care; full recovery expected in most cases |
2.2.2 Why This Matters
Aseptic meningitis following vaccination is a known risk for some live viral vaccines (e.g., measles-mumps-rubella vaccine, particularly the Urabe strain of mumps). For the chikungunya vaccine, this represents a new aspect of a known risk, meaning that while aseptic meningitis was already recognized as a potential adverse reaction, new data have refined our understanding of its frequency, severity, or risk factors.
2.3 Regulatory Action
| Parameter | Details |
|---|---|
| Signal EPITT No | 20250 |
| PRAC Rapporteur | Dirk Mentzer (DE) |
| Action for MAH | Supplementary information requested (submission by 23 February 2026) |
| MAH | Valneva Austria GmbH |
What This Means: The MAH was required to provide additional data to characterize this risk more precisely. This may include:
- Updated cumulative review of all aseptic meningitis cases post-marketing
- Analysis of risk factors (age, sex, underlying conditions)
- Assessment of potential mechanisms (direct viral vs. immune-mediated)
- Evaluation of impact on benefit-risk balance
2.4 Clinical Implications for Healthcare Professionals
| Implication | Action |
|---|---|
| Patient Selection | Assess individual risk factors before vaccination; consider contraindications in patients with history of meningitis or severe vaccine reactions |
| Informed Consent | Counsel patients about the rare risk of aseptic meningitis; provide clear information on symptoms to watch for |
| Post-Vaccination Monitoring | Advise patients to seek medical attention if they develop severe headache, neck stiffness, photophobia, or persistent fever after vaccination |
| Diagnostic Consideration | In patients presenting with meningitis symptoms post-vaccination, consider aseptic meningitis in differential; perform lumbar puncture and consider testing for vaccine-strain virus |
| Reporting | Report any suspected cases of aseptic meningitis following chikungunya vaccination to national pharmacovigilance centres |
2.5 Patient Counseling Points
| Topic | Key Message |
|---|---|
| Risk Awareness | “In very rare cases, this vaccine may cause inflammation of the lining of the brain and spinal cord, called aseptic meningitis.” |
| Symptoms | “Seek medical help immediately if you develop severe headache, stiff neck, sensitivity to light, or persistent fever after vaccination.” |
| Prognosis | “Most people recover fully with supportive care, but it’s important to be evaluated promptly.” |
3. Signal 2: Omalizumab – Acquired Haemophilia
3.1 Background: Omalizumab
Omalizumab is a recombinant humanized monoclonal antibody that binds selectively to human immunoglobulin E (IgE). It is indicated for:
| Indication | Description |
|---|---|
| Severe Persistent Allergic Asthma | Patients with positive skin test or in vitro reactivity to perennial aeroallergens and reduced lung function |
| Chronic Spontaneous Urticaria (CSU) | Patients who remain symptomatic despite H1 antihistamine treatment |
Omalizumab is available as both innovator (Novartis) and biosimilar (Celltrion) products.
3.2 The Signal: Acquired Haemophilia
PRAC identified a signal for acquired haemophilia associated with omalizumab use .
3.2.1 What is Acquired Haemophilia?
Acquired haemophilia is a rare but potentially life-threatening bleeding disorder caused by the development of autoantibodies (inhibitors) against coagulation factor VIII.
| Feature | Description |
|---|---|
| Definition | Bleeding disorder due to autoantibodies inhibiting factor VIII activity |
| Incidence | Approximately 1.5 cases per million population per year |
| Demographics | Bimodal distribution: young women (postpartum) and elderly (both sexes) |
| Underlying Causes | Autoimmune disorders, malignancy, pregnancy, drugs, or idiopathic (50%) |
| Clinical Presentation | Spontaneous bruising, soft tissue hematomas, prolonged bleeding after trauma/surgery; hemarthrosis is rare (unlike congenital haemophilia) |
| Diagnosis | Isolated prolonged aPTT not corrected by mixing study; low factor VIII activity; detectable factor VIII inhibitors (Bethesda assay) |
| Complications | Severe bleeding (retroperitoneal, intracranial, gastrointestinal) in up to 70% of patients; mortality 8-22% |
3.2.2 Drug-Induced Acquired Haemophilia
Several medications have been associated with acquired haemophilia:
| Drug Class | Examples |
|---|---|
| Antibiotics | Penicillins, sulfonamides, cephalosporins |
| Anticonvulsants | Phenytoin, valproate |
| Antipsychotics | Clozapine, risperidone |
| Biologics | Interferon-alfa, fludarabine, and now omalizumab (signal) |
| Others | Methyldopa, levodopa, clopidogrel |
Mechanism: Drug-induced autoimmunity through molecular mimicry, altered immune regulation, or hapten formation.
3.3 Regulatory Action
| Parameter | Details |
|---|---|
| Signal EPITT No | 19385 |
| PRAC Rapporteur | Mari Thörn (SE) |
| Action for MAH | Assess in the next PSUR (submission by 31 March 2026) |
| MAHs | Novartis Europharm Limited, Celltrion Healthcare Hungary Kft. |
What This Means: The MAHs must include a comprehensive analysis of all reported cases of acquired haemophilia in the upcoming Periodic Safety Update Report. This assessment should include:
- Cumulative case review (spontaneous reports, literature, clinical trials)
- Detailed case-by-case evaluation (causality, risk factors, outcomes)
- Analysis of incidence rates (exposure-adjusted)
- Proposed updates to product information if warranted
- Risk minimization measures if needed
3.4 Clinical Implications for Healthcare Professionals
| Implication | Action |
|---|---|
| Awareness | Maintain high index of suspicion for acquired haemophilia in patients on omalizumab presenting with unexplained bleeding or bruising |
| Diagnostic Workup | If suspected, obtain aPTT, mixing study, factor VIII assay, and Bethesda inhibitor assay; consult haematology |
| Differential Diagnosis | Consider other causes of acquired bleeding: vitamin K deficiency, liver disease, disseminated intravascular coagulation (DIC), other factor deficiencies |
| Management | Discontinue omalizumab if suspected; initiate immunosuppression (corticosteroids, cyclophosphamide, rituximab) under haematology guidance; bypassing agents (rFVIIa, aPCC) for severe bleeding |
| Reporting | Report any suspected cases to national pharmacovigilance centres and to the MAH |
| Patient Education | Advise patients to report any unusual bleeding, bruising, or prolonged bleeding after minor cuts |
3.5 Patient Counseling Points
| Topic | Key Message |
|---|---|
| Warning Signs | “Tell your doctor immediately if you notice unusual bruising, bleeding that won’t stop, blood in urine or stool, or severe headache.” |
| Timing | “This reaction can occur at any time during treatment—stay vigilant even if you’ve been on the medicine for a while.” |
| Emergency | “Seek emergency care if you have severe bleeding or signs of internal bleeding (abdominal pain, dizziness, confusion).” |
4. Signal 3: Risankizumab – Pemphigoid
4.1 Background: Risankizumab
Risankizumab is a humanized monoclonal antibody that selectively inhibits interleukin-23 (IL-23) by binding to its p19 subunit. It is indicated for:
| Indication | Description |
|---|---|
| Plaque Psoriasis | Moderate to severe plaque psoriasis in adults who are candidates for systemic therapy |
| Psoriatic Arthritis | Active psoriatic arthritis in adults (alone or with methotrexate) |
| Crohn’s Disease | Moderately to severely active Crohn’s disease after conventional or biologic therapy failure |
4.2 The Signal: Pemphigoid
PRAC identified a signal for pemphigoid associated with risankizumab use .
4.2.1 What is Pemphigoid?
Pemphigoid refers to a group of autoimmune blistering diseases characterized by subepidermal blister formation due to autoantibodies against components of the hemidesmosome.
| Feature | Bullous Pemphigoid | Mucous Membrane Pemphigoid |
|---|---|---|
| Target Antigen | BP180 (collagen XVII), BP230 | BP180, laminin 332, others |
| Clinical Presentation | Tense blisters on normal or erythematous skin; intense pruritus; affects flexural areas, trunk, extremities | Predominantly mucosal lesions (oral, ocular, genital); scarring potential |
| Histopathology | Subepidermal blister with eosinophilic infiltrate | Subepidermal blister with mixed infiltrate |
| Immunofluorescence | Linear deposition of IgG and C3 along basement membrane zone | Linear IgG/IgA/C3 along basement membrane zone |
| Complications | Secondary infection; rare mortality | Ocular scarring leading to blindness; airway compromise |
4.2.2 Drug-Induced Pemphigoid
Several medications have been associated with drug-induced pemphigoid:
| Drug Class | Examples |
|---|---|
| Diuretics | Furosemide, hydrochlorothiazide |
| Antibiotics | Amoxicillin, ciprofloxacin, rifampin |
| Antidiabetics | Dipeptidyl peptidase-4 (DPP-4) inhibitors (vildagliptin, sitagliptin)—well-established class effect |
| Biologics | TNF inhibitors, checkpoint inhibitors, IL-17 inhibitors, and now IL-23 inhibitors (signal) |
| Others | NSAIDs, levodopa, iodinated contrast |
Mechanism: Drug-induced pemphigoid may occur through:
- Molecular mimicry (drug induces cross-reactive antibodies)
- Alteration of immune tolerance (checkpoint inhibitors)
- Direct toxicity to basement membrane components
- Unmasking of cryptic epitopes
4.3 Regulatory Action
| Parameter | Details |
|---|---|
| Signal EPITT No | 20192 |
| PRAC Rapporteur | Liana Martirosyan (NL) |
| Action for MAH | Routine pharmacovigilance |
| MAH | AbbVie Deutschland GmbH & Co. KG |
What This Means: The signal did not warrant immediate regulatory action or product information update. The MAH should continue routine monitoring and include relevant cases in upcoming PSURs. Healthcare professionals should remain vigilant and report suspected cases.
4.4 Clinical Implications for Healthcare Professionals
| Implication | Action |
|---|---|
| Awareness | Be aware of the potential for pemphigoid in patients on risankizumab, particularly those with other risk factors (elderly, concomitant DPP-4 inhibitor use) |
| Differential Diagnosis | Consider drug-induced pemphigoid in patients presenting with new-onset blistering rash; distinguish from psoriasis flare (can be challenging) |
| Diagnostic Workup | Skin biopsy for histopathology and direct immunofluorescence; serum for indirect immunofluorescence and ELISA for BP180/BP230 antibodies |
| Management | If suspected, consider discontinuing risankizumab; initiate topical or systemic corticosteroids under dermatology guidance; other immunosuppressants (dapsone, doxycycline, methotrexate) may be needed |
| Reporting | Report any suspected cases to national pharmacovigilance centres and to the MAH |
4.5 Patient Counseling Points
| Topic | Key Message |
|---|---|
| Skin Monitoring | “Contact your doctor if you develop any new skin rash, blisters, or itching, especially if they don’t look like your usual psoriasis.” |
| Mucous Membrane Symptoms | “Report any mouth sores, eye irritation, or genital lesions promptly.” |
| Timing | “Drug reactions can occur weeks to months after starting treatment—stay alert throughout therapy.” |
5. Comparative Analysis of PRAC Actions
| Signal | Drug | PRAC Action | Timeline | Clinical Severity | Expected Outcome |
|---|---|---|---|---|---|
| Aseptic Meningitis | Chikungunya vaccine (live) | Supplementary information | 23 Feb 2026 | Moderate | Likely product information update |
| Acquired Haemophilia | Omalizumab | Assess in next PSUR | 31 Mar 2026 | High (life-threatening) | Possible product information update |
| Pemphigoid | Risankizumab | Routine pharmacovigilance | Ongoing | Moderate | Continued monitoring |
6. The Pharmacovigilance Framework: Understanding PRAC Recommendations
6.1 Types of PRAC Actions
| Action Type | Description | Implication for MAH |
|---|---|---|
| Supplementary Information Request | MAH must provide specific data within a defined timeframe | Urgent action; data may inform regulatory decision |
| Assessment in Next PSUR | Signal to be evaluated in upcoming Periodic Safety Update Report | Systematic review; may lead to future regulatory action |
| Routine Pharmacovigilance | No immediate action beyond standard monitoring | Continue routine surveillance; report in PSURs |
| Product Information Update | Changes to SmPC and package leaflet | Implement variations as per regulatory procedures |
| Additional Analyses | Agency or Member State to conduct further studies | External research; MAH may need to provide data |
6.2 Procedural Context
For Centrally Authorised Products (CAPs) , PRAC recommendations for regulatory action are submitted to the Committee for Medicinal Products for Human Use (CHMP) for endorsement. For Nationally Authorised Products (NAPs) , recommendations are forwarded to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) for information .
Important Note: MAHs are reminded that in line with Article 16(3) of Regulation (EU) 726/2004 and Article 23(3) of Directive 2001/83/EC, they shall ensure that their product information is kept up to date with current scientific knowledge, including conclusions of assessments and recommendations published on the EMA website .
7. Practical Guidance for Healthcare Professionals
7.1 Recognizing and Reporting Adverse Reactions
| Step | Action |
|---|---|
| 1. Maintain Suspicion | Consider drug-induced aetiologies for unusual presentations |
| 2. Document Thoroughly | Record temporal relationship, dechallenge/rechallenge information, concomitant medications |
| 3. Consult Specialists | Haematology for bleeding disorders; dermatology for blistering diseases; neurology for meningitis |
| 4. Report to Pharmacovigilance Centre | National centres (e.g., MHRA, BfArM, ANSM) or directly to MAH |
| 5. Contribute to Literature | Case reports add to global knowledge base |
7.2 Specific Guidance for Each Signal
| Signal | Red Flags | Diagnostic Steps | Management |
|---|---|---|---|
| Aseptic Meningitis | Headache + neck stiffness + photophobia post-vaccination | Lumbar puncture; CSF PCR for vaccine-strain virus; brain imaging if focal signs | Supportive care; consider antiviral if indicated; report to VAERS/EudraVigilance |
| Acquired Haemophilia | Unexplained bruising, soft tissue haematoma, prolonged aPTT | aPTT, mixing study, factor VIII, Bethesda assay; haematology consult | Discontinue omalizumab; immunosuppression; bypassing agents for severe bleeding |
| Pemphigoid | New blistering rash, pruritus, mucosal lesions | Skin biopsy (H&E + DIF); serum for BP180/BP230 antibodies; dermatology consult | Consider discontinuing risankizumab; topical/systemic corticosteroids |
8. Conclusion: Vigilance in Practice
The February 2026 PRAC meeting highlights the dynamic nature of medication safety and the critical role of pharmacovigilance in protecting patient health. Three distinct safety signals—aseptic meningitis with chikungunya vaccine, acquired haemophilia with omalizumab, and pemphigoid with risankizumab—demonstrate the diverse ways in which adverse reactions can manifest and the varying regulatory responses required.
Key Takeaways for Healthcare Professionals:
- Chikungunya Vaccine: Aseptic meningitis is a rare but known risk; counsel patients appropriately and maintain diagnostic vigilance post-vaccination.
- Omalizumab: Acquired haemophilia is a rare but life-threatening adverse reaction. Maintain high suspicion for unexplained bleeding and consult haematology promptly.
- Risankizumab: Pemphigoid is a potential adverse reaction requiring routine monitoring. Consider drug-induced aetiology in patients presenting with new blistering eruptions.
- Reporting is Essential: Each suspected adverse reaction reported contributes to the global understanding of drug safety and may help identify signals that protect future patients.
- Stay Informed: PRAC recommendations are published regularly on the EMA website. Healthcare professionals should review updates relevant to their practice.
By staying informed of regulatory updates, maintaining clinical vigilance, and reporting suspected adverse reactions, healthcare professionals contribute to the continuous improvement of medication safety for patients across Europe and beyond.
