Published: 16 January 2025

Safety Information

Monitoring communication

Patients should NOT stop using any medicine or medical device subject to a monitoring communication. If you have any concerns with a medicine or medical device you are using, please contact your healthcare professional. A monitoring communication does not mean that the medicine causes an adverse event.

M2 logo Anti-CD20 monoclonal antibodies (rituximab, ocrelizumab, obinutuzumab, ofatumumab) and the possible risk of pyoderma gangrenosum

16 January 2025

Monitoring closes 16 July 2025

Pyoderma gangrenosum (PG), a rare inflammatory skin disease, has been reported internationally during treatment with anti-CD20 monoclonal antibodies (rituximab, ocrelizumab, obinutuzumab and ofatumumab).

The Medicines Adverse Reaction Committee (MARC) reviewed the possible association between PG and anti-CD20 monoclonal antibodies at their 199th meeting in September 2024. They considered that the current evidence for a causal link is weak and recommended that Medsafe publish a monitoring communication to gather more information.

This communication encourages reporting of pyoderma gangrenosum cases that may be associated with an anti-CD20 monoclonal antibody. Anyone can submit a report.

Products affected
More information
Medsafe's actions
Reporting adverse events
References

Products affected

Table 1 below shows the anti-CD20 monoclonal antibody products that are approved and available in New Zealand, along with the approved indications for use and sponsors. Note there is one approved ofatumumab product in New Zealand (Kesimpta), but it is not included in the table because it is not marketed.

Table 1: Anti-CD20 monoclonal antibody products approved and available in NZ

Product name Active ingredient Indicated conditionsa Sponsor
Ocrevus Ocrelizumab Multiple sclerosis – relapsing and primary progressive Roche Products (NZ) Ltd
Gazyva Obinutuzumab Chronic lymphocytic leukaemia
Non-Hodgkin's lymphoma		 Roche Products (NZ) Ltd
MabThera Rituximab Non-Hodgkin's lymphoma
Chronic lymphocytic leukaemia
Rheumatoid arthritis
Granulomatosis with polyangiitis (Wegener's) and Microscopic polyangiitis 		Roche Products (NZ) Ltd
Riximyo Rituximab Non-Hodgkin's lymphoma
Chronic lymphocytic leukaemia
Rheumatoid arthritis
Granulomatosis with polyangiitis (Wegener's) and Microscopic polyangiitis 		Sandoz NZ Ltd
  1. Indicated conditions as per the data sheets, available at: medsafe.govt.nz/Medicines/infoSearch.asp

More information

Pyoderma gangrenosum (PG) presents as a rapidly enlarging, very painful ulcer.1 The lower legs are most frequently affected but it can present anywhere in the body.2 It is a rare disease, with approximately 3 to 10 cases per million people per year.3 PG can affect people of any age but is more common in those aged over 50 years.1 It is frequently associated with systemic conditions, such as inflammatory bowel disease, rheumatoid arthritis and certain blood diseases (eg, leukaemia).1

PG triggers include injury to the skin, surgery or illicit drugs (eg, cocaine).1 It is also associated with some medicines (eg, sunitinib,4 secukinumab,5 azacitidine6). However, some diseases that are treated with anti-CD monoclonal antibodies are risk factors for PG.1 PG can be difficult to diagnose, potentially leading to inappropriate treatment and/or treatment delays.3, 7, 8

The MARC discussed the PG cases reported during treatment with anti-CD20 monoclonal antibodies in the literature and in pharmacovigilance databases. Rituximab and ocrelizumab were the most frequently reported medicines. They noted that reporting rates across this class of medicines appear to be proportionate to use. Cases were predominantly in females in their fifties and involved the vulvovaginal area. To date, no cases have been reported in New Zealand.

The median time to onset of symptoms was approximately 3 years after the start of treatment. The MARC commented that this long onset time may contribute to under-reporting of potential cases. They noted that compared to the use of these medicines, only a small number of PG cases have been reported worldwide. Even after accounting for under-reporting of cases, the risk is low.

Given the small number of cases reported and potential confounding, the MARC considered that the current evidence of a causal association between anti-CD20 monoclonal antibodies and PG is weak.

See the minutes of the MARC meeting and the report presented to the MARC for further details.

See the consumer medicine information (CMI) and data sheets for advice on how to take these medicines and the known side effects.

Medsafe's actions

We are placing this potential safety concern on the Medicines Monitoring (M2 Logo) scheme to encourage reporting of any occurrences of pyoderma gangrenosum with anti-CD20 monoclonal antibodies.

Reporting adverse events

Please report adverse events to medicines (side effects) to the Centre for Adverse Reactions Monitoring (CARM). Anyone can submit a report.

References

  1. Oakley A and Dhawan G. 2015. Pyoderma gangrenosum. In: DermNet updated March 2022. URL: https://dermnetnz.org/topics/pyoderma-gangrenosum (accessed 7 March 2024).
  2. George G, Deroide F and Rustin M. 2019. Pyoderma gangrenosum – a guide to diagnosis and management. Clinical Medicine (London, England) 19(3): 224-8. DOI: 10.7861/clinmedicine.19-3-224 (accessed 5 August 2024).
  3. Maverakis E, Ma C, Shinkai K, et al. 2018. Diagnostic criteria of ulcerative pyoderma gangrenosum: A Delphi consensus of international experts. JAMA Dermatology 154(4): 461-66. DOI: 10.1001/jamadermatol.2017.5980 (accessed 5 August 2024).
  4. Pfizer New Zealand Limited. 2021. Sunitinib Pfizer New Zealand Data Sheet 12 August 2021. URL: https://www.medsafe.govt.nz/profs/Datasheet/s/sunitinibpfizercap.pdf (accessed 14 October 2024).
  5. Novartis New Zealand. 2024. Cosentyx New Zealand 30 May 2024. URL: https://www.medsafe.govt.nz/profs/Datasheet/c/cosentyxinj.pdf (accessed 14 October 2024).
  6. Dr Reddy’s New Zealand Ltd. 2022. Azacitidine Dr Reddy's New Zealand Data Sheet 11 January 2022. URL: https://www.medsafe.govt.nz/profs/Datasheet/a/azacitidineDrReddysinj.pdf (accessed 14 October 2024).
  7. Qureshi A, Persaud K, Zulfiqar S, et al. 2021. Atypical Pyoderma gangrenosum: a case of delayed recognition. Journal of Community Hospital Internal Medicine Perspectives 11(2): 242-8. DOI: https://doi.org/10.1080/20009666.2020.1866250 (accessed 17 April 2024).
  8. Na H, Yan H and CH P. 2023. Misdiagnosis of pyoderma gangrenosum increases medical costs and prolongs hospital stay: A case report (abstract only). The International Journal of Lower Extremity Wounds 22(2): 428-33. DOI: 10.1177/15347346211011870 (accessed 17 April 2024).
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