Hepatitis B vaccination associated with low response in patients with rheumatic diseases treated with biologics.

BACKGROUND: Hepatitis B virus (HBV) vaccination is recommended for non-immunised patients with rheumatic diseases starting biological disease-modifying antirheumatic drugs (bDMARDs). There is some evidence that HBV vaccination is effective in patients under conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), but it is currently unclear whether this also applies to bDMARDs. OBJECTIVES: To assess the efficacy and safety of HBV vaccination in patients with inflammatory arthritides treated with bDMARDs. METHODS: A prospective cohort with inflammatory arthritides treated with bDMARDs, negative for anti-HBs and anti-HBc and never vaccinated for HBV was recruited. Engerix B was administered at 0, 1 and 6 months and anti-HBs was reassessed ≥1 month after last dose. Response was defined as anti-HBs≥10 IU/L and compared against vaccinated healthy controls. Disease flare, serious adverse events and immune-related disorders not previously present were recorded. RESULTS: 62 patients, most treated with TNF inhibitors (TNFi), and 38 controls were recruited. Most patients were taking csDMARDs (67.7%) and were in remission/low disease activity (59.4%). Only 20/62 patients (32.3%) had a positive response to vaccination, in comparison to 36/38 age-matched controls (94.7%, p<0.001). Response was seen in 19/51 patients treated with TNFi (37.3%) and in 1/11 (9.1%) patients treated with non-TNFi (p=0.07), including 1/6 treated with tocilizumab (16.7%). Among TNFi, response rates ranged from 4/22 (18.2%) for infliximab to 8/14 (57.1%) for etanercept. No relevant safety issues were identified. CONCLUSIONS: HBV vaccination response in patients with rheumatic diseases treated with bDMARDs was poorer than expected. Our data reinforce the recommendation for vaccination prior to starting bDMARDs.

Rheumatology practice amidst the COVID-19 pandemic: a pragmatic view.

The coronavirus disease 2019 (COVID-19) pandemic has come with many challenges for healthcare providers and patients alike. In addition to the direct burden it has placed on societies and health systems, it had a significant impact in the care of patients with chronic diseases, as healthcare resources were deployed to fight the crisis, and major travel and social restrictions were adopted. In the field of rheumatology, this has required notable efforts from departments and clinicians to adapt to the novel status quo and assure the follow-up of patients with rheumatic and musculoskeletal diseases. In the present viewpoint, we provide a practical approach to tackle this reality. Key measures include setting up preventive team management strategies, optimising communication with patients and reorganising patient care in all its dimensions. We then anticipate the nuances of rheumatology practice as restrictive measures are progressively lifted, while an effective vaccine is still pending. This includes the need to reimpose the same strategy as further waves unfold. Finally, we look ahead and address the lessons we can incorporate into post-COVID-19 rheumatology.

Tuberculosis under anti-TNF therapy: case series of a center (reporting the experience from the period 2006-2019).

Patients with inflammatory rheumatic diseases refractory to conventional disease modifying antirheumatic drugs (DMARDs)have been treated with biologics for the last two decades. It is also known that patients under biotechnological therapy present a higher risk of developing Tuberculosis (TB).Portugal has now a TB incidence classified as low. National recommendations advise on latent TB screening before the beginning of the biological therapy. This screening consists in the detection of risk factors and/or signs and symptoms of latent TB through clinical history, physical examination, chest X-ray, tuberculin skin test and Interferon Gamma Release Assay (IGRA) test. We describe five clinical cases of patients who underwent biotechnological therapy at our Hospital after 2006 and developed TB.

Efficacy, immunogenicity and cost analysis of a systematic switch from originator infliximab to biosimilar CT-P13 of all patients with inflammatory arthritis from a single center.

Biosimilar drugs are intended to be as effective as the originator product but with a lower cost to healthcare systems. In our center we promoted a switch from originator infliximab (IFXor) to biosimilar infliximab (CT-P13). We analyzed efficacy, safety, immunogenicity and cost savings of switching. Eligible patients were adults with the diagnosis of rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) on therapy with IFXor for at least 6 months and with stable disease activity. Efficacy was measured considering change from baseline in Disease Activity Score in 28 joints (DAS28) for RA and PsA and in Ankylosing Spondylitis Disease Activity Score (ASDAS) for SpA. Disease worsening was considered when an increase of 1.2 from baseline in DAS28 or an increase of 1.1 in ASDAS occurred. Serum IFX levels (sIFX) were dichotomized as therapeutic (between 3-6 µg/mL), low (< 3 µg/mL), and high (> 6 µg/mL). Anti-drug antibody (ADA) levels were dichotomized into detectable (> 10 ng/ml) or non-detectable (< 10 ng/ml). A cost analysis was done based on the purchasing prices of the 2 drugs at our center. During a period of 1 year switch to CT-P13 was performed in 60 patients for non-medical reasons. We had a total of 36 patients with SpA, 16 with RA and 8 with PsA. Disease activity was stable over the observation period and similar to the values observed with IFXor. Median follow-up time was 15 months during which 5 patients stopped CT-P13. Forty two switchers had blood samples collected before and after switch. A total of 27 patients had unaltered sIFX levels and ADA status during follow up. Three patients had detectable ADA at baseline, with low sIFX levels. After switch, ADAs became negative in 2 of those patients, and the other patient kept detectable ADA levels. ADAs became positive in 5 patients after switch. The switch to CT-P13 represented a 26.4 % reduction of costs in the use of IFX therapy in these patients. The switch in routine care of a group of RA, SpA and PsA patients from IFXor to CT-P13 did not affect efficacy, safety, immunogenicity and reduced costs in 26.4%. The observed changes in blood samples were not associated with higher disease activity and did not lead to stopping IFX therapy.

Loss to follow-up in registries of rheumatic patients treated with biologics: a potential information bias in assessing pharmacovigilance and efficacy outcomes.

BACKGROUND: The information associated with loss to follow-up (LFU) patients may affect real-world data evaluation of the use of biologics that is not being adequately captured in registries. METHODS: We identified all patients (Pts) treated with biologics in our center who had no visits registered for more than 6 months, in the Rheumatic Diseases Portuguese Register, Reuma.pt. We retrieved baseline information from Reuma.pt and from the hospital electronic clinical record. We then performed a telephonic interview to characterize the reasons for LFU at our day care unit. For Pts unable to be contacted by telephone a letter of invitation to an appointment at the hospital was sent. RESULTS: From a total of 794 Pts registered in Reuma.pt at our center with active biologic therapy 227 did not have any information registered in the last 6 months. Of this, 36 Pts were on biologic therapy prescribed by other departments and maintained follow-up in these departments. 102 Pts had suspended biologic administration by medical indication and this information was registered in the hospital electronic clinical records but not updated in Reuma.pt. For 89 Pts no information could be retrieved from either the hospital electronic clinical record or Reuma.pt and we classified these Pts as true LFU. 26 of these LFU Pts were being followed up in another Rheumatology center. 26 of the LFU Pts died. 11 Pts had an adverse effect. 4 Pts of the LFU were considering to be in remission. We were not able to contact 15 of the LFU pts. CONCLUSION: Identifying LFU Pts and clarifying the reason for the loss of data in a register contributes to a better knowledge on strategies to discontinue biologics in stable pts, to a better pharmacovigilance of adverse effects and to more efficiency in data capture by registries. Due to data protection reasons it was impossible to have access to the Pts's death certificates.

The Portuguese Society of Rheumatology position paper on the use of biosimilars - 2017 update.

Biosimilars are new and more affordable similar versions of previously approved reference biological drugs. Following the approval of the first monoclonal antibody biosimilar in 2013, the Portuguese Society of Rheumatology issued a position paper on the use of biosimilars in rheumatic conditions covering efficacy, safety, extrapolation, interchangeability, substitution and pharmacovigilance. However, as this is a rapidly evolving field, it was felt that the knowledge and evidence gathered since then justified an update of these statements. Literature searches on these issues were performed and the search results were presented and discussed in a national meeting. Portuguese rheumatologists considered that affordability should be taken into consideration when initiating a biological drug, but other factors were equally important. In patients already on reference biological treatment, switch to a more affordable biosimilar is desirable, provided a set of conditions is rigorously met. Automatic substitution is not acceptable and current evidence is insufficient to support interchangeability. Extrapolation of clinical indications is endorsed by Portuguese rheumatologists, and the statements on safety, pharmacovigilance and traceability are in accordance with the previous position paper.

[Practical guide for the use of biological agents in rheumatoid arthritis - December 2011 update]. / Guia prático de utilização de terapêuticas biotecnológicas na artrite reumatóide - actualização de Dezembro 2011.

The authors review the practical aspects of biological therapy use for rheumatoid arthritis patients, commenting safety issues before and after treatment initiation and the best treatment strategies to optimize efficacy.

[Demineralised cortical bone allografting in femoral head necrosis]. / Aloenxerto ósseo cortical desmineralizado na cirurgia da osteonecrose asséptica da cabeça femoral.

We report the clinical and biological results of the surgical treatment of a femoral head osteonecrosis, Ficat classification stage III, in a 53 year old patient. The procedure included core decompression followed by insertion of a superficial demineralised and processed fibular bone allograft. A cemented total hip arthroplasty was performed at nine years follow-up. The histomorphological study of the excised femoral head showed the incorporation of the bone allograft. Although core decompression of the femoral head has been used in precollapse lesions, Ficat stage I and II, its combination with fibular allografting allowed the postponement of total hip prosthesis implantation for nine years. In this clinical case, the implantation of a total hip arthroplasty, as a primary surgical treatment, would also have been an alternative procedure, if it had only been considered the patient;s age and osteonecrosis extension.

[Cyclophosphamide induced amenorrhoea in pre-menopausal women with systemic lupus erythematosus]. / Amenorreia induzida por ciclofosfamida em doentes pré-menopáusicas com lúpus eritematoso sistémico.

OBJECTIVES: To determine the frequency of ovarian failure in pre-menopausal women after cyclophosphamide (cyc) treatment for systemic lupus erythematosus (SLE); identify risk factors for this complication; estimate the occurrence and viability of pregnancy during and after treatment. METHODS: Review of the data of women treated with intravenous cyc in the department of Rheumatology of Hospitais da Universidade de Coimbra, updated by interview. Information on demographic features; gynaecologic and obstetrical history; characteristics of the disease; duration and side effects of treatment were obtained. Ovarian failure was defined as a lack of menses for, at least, four months and the diagnosis was confirmed by hormonal measurements. RESULTS: Nineteen pre-menopausal women were treated with intravenous cyc in our department. The mean age at the time of cyc initiation was 28.4 years. Lupus nephritis was the most common indication for cyc treatment (89.5%). The mean number of pulses was 9.3 over a period of 16.8 months. The mean cumulative dosage was 6.973 mg. Three patients developed ovarian failure. Those women were older than the others (P=0.0016). One patient became pregnant while on treatment. Two women delivered healthy children after cyc withdrawal. CONCLUSION: Ovarian failure developed in 15.8% of our patients. As described in the literature, the age at cyc initiation appears to be a determinant risk factor. Pregnancy may occur during cyc therapy, and thus, an effective contraception is mandatory. After cyc withdrawal, pregnancy is possible with a favourable outcome.

[Surgical procedures for treatment of the rheumatoid knee]. / Procedimentos Cirurgicos do Joelho na Artrite Reumatoide.

In the last decade considerable modifications in the surgical procedures recommended for the treatment of rheumatoid knee have been observed. This was due to all the medical developments achieved in pharmacology and therapeutic as well as a significant quality improvement of the rheumatologist s intervention. The synovectomy and namely the total knee arthroplasty represent the most commonly procedures used in the surgical treatment of the rheumatoid knee. An arthroscopic followed by a radionuclide synovectomy can be an appropriate treatment in a knee with an inflammatory arthritis Larsen radiograph grade I II . The ideal patient for synovectomy must present an early disease absence of deformity or instability good range of motion and preserved articular cartilage. On the other hand a total knee arthroplasty represents the only possible operation to treat a rheumatoid knee with a severe bone and cartilage damage Larsen radiograph grade IV V including younger patients. Total knee arthroplasty is actually a successful operation providing pain relief and the restoration of the function. Nevertheless the excellent good short and medium-term results achieved do not resist over time. Similarly to what happens with every other arthoplasty joint replacements the particules that come from the wear of the biomaterials included in its composition are the cause of biological intolerance reactions which can lead to the need of a new implant. The replacement prosthesis raises technical issues related to the reconstruction of bone mass losses where the cryopreserved bone allografts can be recommended.

[Tuberculosis in rheumatic patients treated with tumour necrosis factor alpha antagonists: the Portuguese experience]. / Tubereulose em doentes reumáticos tratados com antagonistas do factor de necrose tumoral alfa: a experiência Portuguesa.

In Portugal, 13 cases of tuberculosis (TB) were reported, in the period between 1999 and 2005, in 960 patients exposed to anti-TNFalpha treatment (1.35%), 8 females and 5 males. Mean age was 46.7 +/- 13.8 years. 9 patients had rheumatoid arthritis (RA), in 639 exposed patients (1.4%), 3 had ankylosing spondylitis (AS), in 200 exposed patients (1.5%) and 1 had psoriatic arthritis (PA), in 101 exposed patients (1%). The anti-TNFa used was in 8 cases infliximab (in 456 patients exposed, 1.5%), in 4 adalimumab (in 171 patients exposed, 2.3%) and in 1 etanercept (in 333 exposed, 0.3%). Treatment with a biological agent was started 11.1 +/- 8.7 months (min 3 and max 50) before TB onset. Tuberculin skin test (TST) was performed in 9 out of the 13 patients (the other 4 had started biological therapy before 2002). In 3 cases the TST response was 0 mm, in 3 less than 10 mm, in one was 14 mm and in two 20 mm. In the 3 cases with a TST response superior to 10 mm, isoniazid treatment 300 mg/d was prescribed, during 9 months. The time between first symptoms and TB diagnosis was 2.6 +/- 2.9 months. TB involvement was pulmonary in 6 patients, lymph node disease in 2, peritoneal and pulmonary in 2, osteoarticular in one case, lymph node disease and splenic in another and miliar TB in the last case. One death was reported; all of the other cases had a good outcome after anti-TB treatment. In two cases (one treated with adalimumab and the other with infliximab), paradoxical response to treatment occurred. None of the patients has restarted biological therapy after TB treatment.