Carlumab

Ankylosing spondylitis (AS) and osteoporosis (OP) are both prevalent illnesses in spine surgery, with OP being a possible consequence of AS. However, the mechanism of AS-induced OP (AS-OP) remains unknown, limiting etiologic research and therapy of the illness. To mine targetable medicine for the prevention and treatment of AS-OP, this study analyzes public data sets using bioinformatics to identify genes and biological pathways relevant to AS-OP.

First, text mining was used to identify common genes associated with AS and OP, after which functional analysis was carried out. The STRING database and Cytoscape software were used to create protein-protein interaction networks. Hub genes and potential drugs were discovered using drug-gene interaction analysis and transcription factors-gene interaction analysis.

The results of text mining showed 241 genes common to AS and OP, from which 115 key symbols were sorted out by functional analysis. As options for treating AS-OP, protein-protein interaction analysis yielded 20 genes, which may be targeted by 13 medications.

Carlumab, bermekimab, rilonacept, rilotumumab, and ficlatuzumab were first identified as the potential drugs for the treatment of AS-OP, proving the value of text mining and pathway analysis in drug discovery.

The objective of this study was to determine the safety and efficacy of carlumab in the treatment of idiopathic pulmonary fibrosis (IPF).A phase 2, randomised, double-blind placebo-controlled dose-ranging study was conducted in patients with IPF (n=126). Patients were randomised to carlumab (1 mg·kg−1, 5 mg·kg−1, or 15 mg·kg−1) or placebo every 4 weeks. The primary endpoint was the rate of percentage change in forced vital capacity (FVC). Secondary endpoints were time to disease progression, absolute change in FVC, relative change in diffusing capacity of the lung for carbon monoxide (DLCO), and St George's Respiratory Questionnaire (SGRQ) total score.Due to a pre-planned, unfavourable interim benefit–risk analysis, dosing was suspended. The rate of percentage change in FVC showed no treatment effect (placebo −0.582%, 1 mg·kg−1−0.533%, 5 mg·kg−1−0.799% and 15 mg·kg−1−0.470%; p=0.261). All active treatment groups showed a greater decline in FVC (1 mg·kg−1−290 mL, 5 mg·kg−1−370 mL and 15 mg·kg−1−320 mL) compared with placebo (−130 mL). No effect on disease progression,DLCO, infection rates or mortality was observed. SGRQ scores showed a nonsignificant trend toward worsening with active treatment. Unexpectedly, free CC-chemokine ligand 2 levels were elevated above baseline at both 24 and 52 weeks. A higher proportion of patients with one or more serious adverse events was observed in the 5 mg·kg−1group (53.1%) compared with 1 mg·kg−1(15.2%), 15 mg·kg−1(21.9%) and placebo (46.4%), although no unexpected serious adverse events were noted.Although dosing was stopped prematurely, it is unlikely that carlumab provides benefit to IPF patients.