Successful use of tocilizumab in a patient with psoriatic arthritis

Sir, PsA comprises a chronic inflammatory seronegative arthropathy that is associated with psoriasis [1]. Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the IL-6 receptor [2]. We describe the successful use of TCZ in a patient diagnosed with PsA. A 57-year-old woman presented with an 8-year history of refractory PsA. At the time of diagnosis, she fulfilled the CASPAR criteria [3], with a symmetrical rheumatoid distribution of joint involvement. A borderline positive RF at 1/32 and negative anti-cyclic citrullinated peptide antibodies were noted (anti-nuclear antibody 1/100, homogeneous pattern; no extractable nuclear antigen detected). Plain radiographs of the hands and feet showed no evidence of established erosive disease. Her psoriasis was mild and only necessitated topical treatment. Historically the patient had been on several DMARDs (reason for discontinuation in parentheses), namely, MTX (gastrointestinal intolerance), SSZ and LEF (both due to lack of significant efficacy). Previous biologic therapy included etanercept, which was stopped due to secondary inefficacy after 6 months of treatment. Switching to an alternative anti-TNF agent was precluded due to the local care provider following national UK guidance from the National Institute of Clinical Excellence. However, an application was approved to treat this patient with rituximab, but unfortunately there was no clinical response after one cycle and it was thus deemed to have failed due to primary inefficacy. Meanwhile, due to locking and significant functional impairment of finger flexion, the patient required surgery to the left hand for carpal tunnel decompression, synovectomy and repair/grafting of the flexor digitorum profundus. An application was made and accepted to treat the patient with i.v. TCZ (8 mg/kg), which was commenced every 4 weeks. MTX 15 mg weekly was continued throughout. Prior to commencement of TCZ, the patient had nine tender joints, eight swollen joints, a global health visual analogue scale (VAS) of 70 and was significantly functionally impaired. After the third infusion, the patient had (and maintained after 15 months) an excellent response with 0 tender joints, 0 swollen joints and a global health VAS of 20. It is interesting to note that this woman has never had a significant CRP rise in her disease course, as is not infrequently observed in PsA. However, since commencement of TCZ, both ESR (31 to 10 mm/h) and CRP (1.2 to 0.5 mg/l) have decreased. Haemoglobin has improved (11.4 to 12.1 g/dl) and liver function has remained within the normal range. An increase in low-density lipoprotein (LDL) cholesterol to 8.1 mmol/l and a total high-density lipoprotein (HDL) cholesterol:cholesterol ratio of 7.4 have been noted, in keeping with treatment on TCZ. TCZ is approved for the treatment of RA and other inflammatory diseases. High levels of the IL-6 pro-inflammatory cytokine have been detected in psoriatic skin lesions and in the synovial tissues of patients with PsA [1, 4]. IL-6 was initially identified as a factor in B cell differentiation [2], but is now thought to influence T cell development, including differentiation into Th17 cells, which are implicated in autoimmune diseases including PsA [1, 4]. A recent case series reported two PsA patients who were both treated with TCZ for 6 months. Despite a complete normalization in the serum CRP in both patients, there was no improvement observed in either the joint or skin disease [5]. To our knowledge, this is the first successful case of TCZ used in a patient with PsA. We are confident that with the lack of inflammatory response or convincing erosions, and despite the weakly positive RF, the clinical phenotype was in keeping with PsA rather than RA. There is a theoretical rationale for the potential efficacy for TCZ in PsA. A pilot study investigating TCZ in PsA is currently in progress; however, the Phase 3 trials of TCZ in axial SpA have thus far been disappointing. Inhibition of the IL-6 receptor by TCZ may be worth considering as a therapeutic target in PsA where patients have failed anti-TNF therapy. Disclosure statement: H.