Adverse drug reactions of itolizumab in COVID-19 patient: A case report

Ziauddin Mohammed¹, Kandi Suryachandra², Manoj P Dandekar²,  
¹ Department of Clinical Pharmacology, Apollo Hospitals, Jubilee Hills, Hyderabad, Telangana, India
² Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India

Correspondence Address:
Manoj P Dandekar
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana
India

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A newly detected coronavirus disease 2019 (COVID-19) has been spread in most countries. The severe COVID-19 manifestations were cytokine release syndrome (CRS), i.e., uncontrolled levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6, and interferon-gamma (IFN-γ) cytokines, and its fatal form is secondary hemophagocytic lymphohistiocytosis. Thus, the reversal of CRS in COVID-19 patients is an important step to halt the progression of pulmonary and systemic complications.[1] The anticytokine therapy has been the preferred treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The rampant COVID-19 pandemic imposed novel treatment strategies to manage the disease's severity and mortality. Itolizumab, anti-CD6 humanized IgG1 mAb, is one such clinical agent, which has been employed to decrease the mortality of severely infected patients.

In India, itolizumab is an approved safe drug for managing psoriasis and rheumatoid arthritis.[2] It suppresses the activation of complementary immune reactions by inhibiting the major pathways that lead to an extensive cytokine release. Thus, the Drugs Controller General of India has approved the emergency use of itolizumab for the management of CRS in patients with moderate-to-severe acute respiratory distress syndrome following SARS-CoV-2 infection.[3] Itolizumab modulates immune responses by selectively inhibiting CD6 which subsequently downregulates the production of proinflammatory cytokines such as IFN-γ, IL-6, TNF-α, and T-cell infiltration and adhesion molecules at inflammatory sites.[4] Therefore, it has been anticipated that itolizumab, by preventing the release of proinflammatory mediators, may impart beneficial effects in patients with severe COVID-19 infection. While itolizumab infusion-related reactions such as wheezing, dyspnea, flushing, nausea, urticaria, cough, chills, rigor, pruritus, dizziness, headache, rash, hypersensitivity, and hypertension are known,[5] these reactions suggested to controlled with premedication and slow infusion rate. Moreover, the safety and efficacy profile is not thoroughly tested in COVID-19 patients.

In addition to respiratory and urinary tract infections, SARS-CoV-2-infected patients also showed an increased risk of bacterial infections. In such cases, treatment with itolizumab may predispose to serious infections. In clinical studies, 4-week treatment with itolizumab showed tubercular lymphadenitis in a tuberculosis patient and septic arthritis in another case. Administration of itolizumab has also been cautioned in immunocompromised patients. Moreover, itolizumab treatment is not recommended for patients with a history of hypersensitivity reaction to any murine proteins and severe allergy. Therefore, itolizumab infusion is recommended to give under the proper invigilance of the medical practitioners and should exercise caution before, during, and posttherapy in patients with a known history of repetitive infections or any other underlying diseases. It is also advised that, in case of the occurrence of any new infection or activation of latent infection, itolizumab treatment should be discontinued immediately. In this case report, we highlighted the clinical manifestations of itolizumab, and adverse drug reactions (ADRs) noted in a 67-year-old male COVID-19 patient.

A 67-year-old male patient was admitted to the hospital with worsening fever, dry cough, and respiratory distress symptoms. The patient was also suffered from other comorbidities such as diabetes and hypertension. Based on his COVID-19 symptoms, he was referred for SARS-CoV-2 testing. As suspected, SARS-CoV-2 virus infection was detected in his nasopharyngeal swab samples. During the physical examination, an elevated body temperature and respiratory rate (>38/min) and low saturation levels of peripheral oxygen were noted. Based on his laboratory reports and clinical signs, he was diagnosed as a covid-19-positive case. As per COVID-19 protocol, the patient received the standard care of treatment, including noninvasive ventilation to maintain oxygen saturation. Due to the detection of CRS, an itolizumab injection was prescribed for the patient. As required, premedication of hydrocortisone injection (100 mg) and pheniramine injection (30 mg) was started 30 min before slow infusion (25 mL/h) of itolizumab. However, within 5 min of itolizumab injection, the patient developed ADRs such as shivering, chills, and cold, along with a profound reduction in oxygen saturation levels.

Due to the above-mentioned ADRs, itolizumab infusion was immediately discontinued and given symptomatic treatment. While symptomatic treatment and stoppage of itolizumab infusion rescinded the itolizumab-generated ADRs, breathlessness, fever, and dry cough persisted for 2–5 days. The patient also complained about gastrointestinal disturbances such as nausea, vomiting, and diarrhea. The inflammatory and coagulation biomarkers recorded a day before and after itolizumab infusion are indicated in [Table 1]. A dramatic reduction of C-reactive protein was observed (111 μg/mL vs. 13.8 μg/mL) following 24 h post-itolizumab treatment; however, other inflammatory and coagulation biomarkers, as indicated in [Table 1], remained unaffected.{Table 1}

The serious ADRs, observed in ~7% of hospital admissions, are the sixth leading cause of death among hospitalized patients. While ADRs developed by itolizumab treatment were resolved after the withdrawal of itolizumab infusion and symptomatic treatment, we feel that more clinical evidence is required for understanding the safety profile of itolizumab treatment in COVID-19 patients or any other conditions.

Financial support and sponsorship

KS and MPD want to thank the DoP and NIPER, Hyderabad, for support in the form of salary and fellowship.

Conflicts of interest

There are no conflicts of interest.

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