Renato De Stefano

Switch from infliximab to infliximab biosimilar: efficacy and safety in a cohort of patients with different rheumatic diseases

Dear Editor in Chief We read with great interest the manuscript by Nikiphorou et al. describing the effectiveness of infliximab-biosimilar CTP13 (INB) used as a switch from Remicade® (Janssen Biotech, Inc., Horsham, PA, USA) (infliximab (INX)) in patients with different established rheumatic diseases [1]. Thirty-nine patients on INX were switched to biosimilar after a mean time (SD) of 4.1 (2.3) years. The authors reported that INB clinical effectiveness, during the first year of switching, was comparable to INX in both the patient-reported outcomes and disease-activity measures, with no immediate safety signals. Eleven patients (28.2%) discontinued INB due to INX antibodies detected prior to INB infusion (3/11), latent tuberculosis (1/11), new-onset neurofibromatosis (1/11), and subjective reasons with no objective deterioration of disease (6/ 11). The authors suggested that subjective reasons, such as negative expectations, played a key role among INB discontinuations. In this regard, we report herein our experience in a cohort of 23 patients followed in our unit for different rheumatic diseases and switched, for local regulatory issues, to INB (Inflectra®) after amean time (SD) of 71.65 (44.40) months on INX (Remicade). More in detail, 11 out of 23 had psoriatic arthritis (7 with peripheral and 4 with axial involvement), 8/23 ankylosing spondylitis, 2/23 rheumatoid arthritis, 2/23 Crohn’s disease and associated axial spondyloarthritis, and 1/23 Behçet’s disease and associated axial spondyloarthritis. At the time of the switch, all of the patients were in complete disease remission on INX at a dose of 5 mg/kg every 8 weeks. After a mean time of 1.71 months (range 1–2) from the start of INB a disease relapse occurred in 7 out of 23 patients (30.43%). Their mean (SD) duration of previous INX treatment was 62.28 (49.95) months. Table 1 summarizes the clinical, demographic, and therapeutic data of the 7 subjects unresponsive to INB. INB was then suspended and IFX was readministered in all 7 patients at a dose of 5 mg/kg every 8 weeks, in association with a tapering dose of oral corticosteroids. In 5/7, the readministration of INX promptly led to a remarkable clinical improvement (4/5), or at least a partial one (1/5), with a significant decrement of the disease activity indexes. No amelioration was observed in 2/7 subjects. Among the 16 patients that were still on treatment with INB, 7 of them were under close observation and monitoring for uveitis relapse (1/7), recurrence of psoriatic lesions (1/7), arthralgia (4/7), and referredworsening of global quality of life (1/7). No changes in the response to treatment were observed in 9 out of 23 subjects (39.13%). INB was well tolerated and no adverse events were noted. In PLANETAS and PLANETRA studies, INB demonstrated equivalent efficacy to INX at 30-week follow-up, with a comparable pharmacokinetic profile and immunogenicity both in patients affected by ankylosing spondylitis (AS) and rheumatoid arthritis (RA) [2,3]. INB efficacy and safety have been confirmed also in the extension of the PLANETAS study in AS at 54-week follow-up [4]. Nevertheless, data on the effectiveness of the switch from INX to INB in patients in a stable disease remissionwhile on IFX are scarce, and future studies are needed. For the above reason, real-life data should be welcome, even though from uncontrolled series, until further trials are performed. In our cohort of patients, 30% of subjects switched from IFX to INB while in disease remission showed a rapid worsening of disease activity indexes. Moreover, 30% of patients still on treatment with INB were under evaluation for the potential reduction of the interval between INB administrations either the potential increase of INB dosage or a further switch from INB to IFX, due to a suspected lack of efficacy. Overall, it is unlikely that in our cohort of patients, only subjective reasons have played a role in the poor outcome observed in most subjects. Indeed, we did not observe any change in the response to treatment in only 40% of cases. Limitations of our study were the small number of patients, the absence of a control group, and the short-

Punch biopsy for fat tissue collection in amyloidosis: is it time to stop needle aspiration?

SIR, Amyloidosis is a heterogeneous group of diseases that share the deposition of amyloid fibrils in organs and tissues, with the same characteristic cross-b-sheet secondary structure, independent of their protein primary structure. More than 30 unrelated autologous proteins can produce systemic amyloidoses, either localized or systemic. The various forms differ in pathogenesis and prognosis, but usually show overlapping clinical manifestations, making their differentiation on clinical grounds very difficult. Precise amyloid typing is crucial for adequate treatment of patients because the various forms require different approaches, which can range from autologous stem cell transplantation in amyloid light-chain (AL) amyloidosis to liver transplantation in transthyretin amyloidosis. The diagnosis and classification are based on histological demonstration of amyloid deposits and characterization of the amyloid precursor [1, 2]. Rectal biopsy has traditionally been the recommended method of screening for amyloidosis. However, since 1973, abdominal fat pad aspiration by fine needle has superseded rectal biopsy as the simplest, fastest and most acceptable way to screen for amyloid, when a systemic form is suspected, being a convenient alternative to organ biopsy [3, 4]. The resulting tissue smear is examined by polarized light microscopy after Congo red staining, in order to detect the presence of amyloid. The second step is to identify the amyloidogenic protein, in order to unequivocally establish the type of amyloidosis. Its sensitivity ranges between 54% and 82%. It can be done at outpatient clinic and requires no technical expertise [4]. Abdominal fat tissue can be aspirated with a 16gauge needle connected to a 10-ml syringe [5]. Although it is safe and reliable, fat aspiration by needle does not yield enough tissue for evaluation in some cases, and its low sensitivity could be related to the possible impact of the size of the needle used for aspiration [6]. Furthermore, there is a need for multiple aspirations (at least three) from different places, especially in patients with a thin abdominal wall. Smith et al. [7] first described in 1986 the usefulness, simplicity and reliability of using a 3.0 mm punch biopsy for collecting skin plus s.c. fat, needed for gas chromatographic analysis of fatty acids. Bogov et al. [8] in 2008 described their positive experience of s.c. fat biopsy to diagnose amyloidosis, made by scalpel and not by punch. We describe a single-centre experience of s.c. fat biopsy, performed by punch. Between March 2012 and December 2014, we performed 138 biopsies at outpatient clinic. All patients (84 female and 54 male, mean age 56.2 years) required such a diagnostic procedure, in order to exclude amyloidosis secondary to various rheumatological conditions, including RA, Behçet’s syndrome and autoinflammatory diseases. In addition, the reliability for amyloid detection in fat samples obtained by punch biopsy was evaluated in comparison with fat specimens obtained from May 2010 to March 2012 by fine needle aspiration technique at our clinic. The biopsy site was prepared with three betadine scrubs and covered with a fenestrated sterile drape. The dermis at the biopsy site (at the right anterior axillary line at the level of the umbilicus) was infiltrated with 0.5 ml of 1% lidocaine followed by injection of 4 ml in the very superficial layers of adipose tissue immediately below the skin (no more than 1 cm deep). Punch biopsy was performed using a circular blade (3.0 mm in diameter) attached to a pencil-like handle. The instrument was rotated down through the epidermis and dermis and into the s.c. fat (Fig. 1A). Punch biopsy yields a cylindrical core of tissue that requires gentle handling (usually with a needle) to prevent a crush artefact at the pathological evaluation. The biopsy site was closed with a single absorbable suture (Vicryl 3-0). Because linear closure was performed on the circular defect, stretching the skin before performing the punch biopsy allows the relaxed skin defect to appear more elliptical and makes it easier to close. The skin was stretched perpendicular to the relaxed skin tension lines, so that the resulting elliptical wound and closure were parallel to these skin tension lines. This modified method does not require any special preparations, materials or consumables. It is easily performed and can be applied in all conditions, including patients with disturbances of coagulation. It generally produces only a minimal scar, and no patients experienced adverse events related to the biopsy; only mild bruising was observed in few patients. We did not observe any site infection; only seven patients reported local transient (<48 h) paraesthesia. The fat tissue obtained by the afore-mentioned procedure is significantly richer in volume in comparison with the fat obtained by needle aspiration (Fig. 1B); in addition, this procedure by punch is able to provide an amount of histologically wellpreserved fat tissue. All of the samples obtained by punch biopsy (n = 138) were suitable for pathological evaluation, compared with 74 of 96 samples (78%) obtained by fine needle aspiration. In conclusion, punch biopsy could represent a quick, cheap and simple procedure for fat collection for identification of amyloid deposits.

Synovial Leishmaniasis: Clinical Images: Synovial leishmaniasis

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