Anti-IL17 antibody Secukinumab therapy is associated with ossification in giant cell tumor of bone: a case report of pathologic similarities and therapeutic potential similar to Denosumab

Abstract

Background Giant cell tumor of bone is a benign, locally aggressive neoplasm. Surgical resection is the preferred treatment method. However, for cases in which resection poses an increased risk to the patient, denosumab (anti-RANKL monoclonal antibody) is considered. Secukinumab is an anti-IL-17 antibody that is used in psoriatic arthritis to reduce bone resorption and articular damage. Case presentation One case of giant cell tumor of bone (GCTB) in a patient treated with secukinumab for psoriatic arthritis demonstrated findings significant for intra-lesional calcifications. Histologic examination showed ossification, new bone formation, and remodeling. A paucity of osteoclast type giant cells was noted. Real-time quantitative polymerase-chain-reaction (qRT-PCR) analysis revealed decreased osteoclast function compared to treatment-naive GCTB. Conclusions Secukinumab may play a role in bone remodeling for GCTB. Radiologists, surgeons, and pathologists should be aware of this interaction, which can cause lesional ossification. Further research is required to define the therapeutic potential of this drug for GCTB and osteolytic disease.

Current Concepts in the Treatment of Giant Cell Tumors of Bone

“…Given that GCTB is generally diagnosed in women of childbearing age, this important point should be investigated in detail in the future. Recently, Chandler et al [130] reported secukinumab (anti-IL-17 antibody) treatment for psoriatic arthritis with significant intralesional calcifications in a patient with GCTB. Histological examination revealed ossification, new bone formation, and remodeling [130].…”

“…Recently, Chandler et al [130] reported secukinumab (anti-IL-17 antibody) treatment for psoriatic arthritis with significant intralesional calcifications in a patient with GCTB. Histological examination revealed ossification, new bone formation, and remodeling [130]. A paucity of osteoclast-type giant cells has also been reported [130].…”

“…Histological examination revealed ossification, new bone formation, and remodeling [130]. A paucity of osteoclast-type giant cells has also been reported [130]. Because secukinumab has much milder adverse effects, including nasopharyngitis, headache, nausea, diarrhea, and pyrexia, and is not contraindicated in pregnant patients [131,132], it may be an alternative treatment to denosumab.…”

Effects of IL-17 Inhibition with Secukinumab in Experimental Periodontitis

“…In an experimental model of myocardial brosis in rats, secukinumab administration resulted in a decrease in RANKL levels in cardiac tissues [25]. In a recent case report of giant cell bone tumor, it was reported that secukinumab administration caused a decrease in RANKL levels in bone tissue [41]. In this study, it was observed that secukinumab administration caused an increase in RANKL levels in periodontal tissues, although not statistically signi cant.…”

Secukinumab Loss of Efficacy Is Perfectly Counteracted by the Introduction of Combination Therapy (Rescue Therapy): Data from a Multicenter Real-Life Study in a Cohort of Italian Psoriatic Patients That Avoided Secukinumab Switching

“…Interestingly, real-life data are more encouraging with 82.2% maintained PASI75, 75.3% PASI 90 and 64.4% PASI100 [52]. At the moment the pathogenetic mechanism of secukinumab-related loss of response remains unknown and several hypothesis are present in literature: anti-drug antibodies [53], increased production of TNF-α [46], changes in lifestyle [54][55][56][57], lack of compliance [58] and comorbidities [59]. Thus, different combination therapies may help to counteract the intricate and partially unknown mechanisms of secukinumab secondary failure.…”