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We read with interest the relevant article by Kostine et al1 describing the specific concerns for the diagnosis and management of rheumatic immune-related adverse events (irAEs), which are caused by immune checkpoint inhibitor (ICI) therapy. The authors recommend to consider glucocorticoid treatment if rheumatic irAEs are not sufficiently controlled by symptomatic treatment. The authors propose that systemic glucocorticoids should be promptly tapered to ≤10 mg predniso(lo)ne equivalent per day, since higher doses might potentially limit the efficacy of ICI therapy. One of the the most common rheumatic irAEs is a polymyalgia rheumatica-like syndrome (ICI-PMR). Prior reports indicate that ICI-PMR is typically treated with 12.5–25 mg prednisolone per day,2 3 which is standard practice for regular PMR.4 We here propose to use lower doses of prednisolone (ie, 5–7.5 mg per day) for patients presenting with ICI-PMR.
We evaluated the treatment requirements of six consecutive patients with ICI-PMR (online supplementary table 1), of whom the clinical and imaging findings were recently reported.5 ICI therapy led to complete cancer remission (n=1), partial remission (n=4) or stable disease (n=1). ICI therapy was eventually discontinued in one patient (patient 6) due to cancer progression. Another patient (patient 2) showed oligoprogression of the cancer. This could be managed with radiotherapy, while ICI therapy was continued. The other patients showed a sustained tumour response ranging from >10 to >24 months after initiation of ICI therapy.
ICI therapy was briefly interrupted in one patient on the diagnosis of ICI-PMR, but continued in all other patients. One subject (patient 4) could be managed with nonsteroidal anti-inflammatory drug (NSAID) treatment only (figure 1A). Two subjects (patients 2 and 3) required a prednisolone dose of 5–7.5 mg per day (figure 1A; online supplementary figure 1, showing patients 3, 5 and 6). Two other subjects (patients 1 and 5) briefly required 15 mg of prednisolone per day. Patient 1 started with 15 mg prednisolone per day, but this could be tapered to 7.5 mg within 2 weeks. Patient 5 was initially treated with 7.5 mg prednisolone per day; but this dose was promptly increased to 15 mg after 1 day and could already be decreased to 7.5 mg after 3 days. One subject (patient 6) received methotrexate as steroid-sparing disease-modifying antirheumatic drug (DMARD) (online supplementary figure 1). Patient 6 initially received 7.5 mg prednisolone equivalent per day due to hypophysitis/adrenal insufficiency; and this was raised to 10 mg prednisolone equivalent per day when ICI-PMR was diagnosed. Due to ongoing disease activity and concerns regarding the potential effect of higher glucocorticoid doses on the efficacy of ICI therapy, a decision was made to add methotrexate to the treatment. The patient eventually died of infection after initiation of chemotherapy.
Prednisolone-free remission was obtained in three subjects (figure 1A). The ICI-PMR went into remission in patient 4 despite continuation of ICI therapy. Patient 2 reached prednisolone-free remission shortly after completion of ICI therapy. Patient 1 reached prednisolone-free remission at 1 year after the final ICI infusion. A [18F]-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan was performed during prednisolone-free remission in two subjects (figure 1B). These follow-up scans showed markedly lower FDG uptake scores when compared with the previously reported scans obtained at the diagnosis of ICI-PMR.5 Thus, the FDG-PET/CT scan confirmed that the ICI-PMR had subsided in both patients.
In conclusion, ICI-PMR may require lower doses of prednisolone than recommended by clinical guidelines for regular PMR.4 If systemic glucocorticoids are needed, a starting dose of 5–7.5 mg prednisolone per day might be sufficient in a substantial part of patients. Prompt response evaluation will identify patients in which the treatment should be stepped up. This approach will limit the use of prednisolone doses that might possibly compromise the efficacy of ICI therapy. As recently proposed by others,6 ICI therapy should not necessarily be discontinued in patients with ICI-PMR.
Contributors KSMvdG and EB contributed to conception or design of the work. KSMvdGG and RHJAS contributed to acquisition of data. All authors contributed to analysis or interpretation of data. All authors were involved in drafting of the work or revising it critically for important intellectual content. All authors provided final approval of the version published. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding KSMvdG work was supported by the Mandema Stipend. EB has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement 668 036.
Competing interests KSMvdG and EB as employees of the UMCG received speaker/consulting fees from Roche that were paid to the UMCG. TJNH as employee of the UMCG received sponsoring/research fee/advisory board fee/other income from BMS, AZD, Merck, Boehringer, Pfizer, Eli Lilly, Roche, Platform immunotherapy and CANCER-ID. SFO received research grants from Novartis and Celldex, paid to the institution.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval This study was performed in accordance with the declaration of Helsinki. The study was approved by the Medical Ethical Committee of the UMCG. All patients provided written informed consent.
Provenance and peer review Not commissioned; internally peer reviewed.