[Janus kinase inhibitors : new perspectives for precision medicine ?] / Inhibiteurs des Janus kinases : nouvelles perspectives pour la médecine de précision ?

Janus kinase inhibitors (JAKi), such as tofacitinib, baricitinib, upadacitinib or ruxolitinib, are small molecules active on specific intracellular targets and used orally for the treatment of autoimmune or myeloproliferative diseases. Their remarkable therapeutic efficacy is offset by a significant risk of toxicities, essentially dose-dependent and a variable pharmacokinetic profile. The JAKi represent a new therapeutic armamentarium for treating autoimmune, myeloproliferative and inflammatory diseases (incl. COVID-19), but require thorough treatment individualization and close monitoring. Therapeutic Drug Monitoring (TDM) of JAKi could allow a personalized prescription and improve the efficacy-toxicity profile.

Les inhibiteurs des Janus kinases (JAKi), tels que le tofacitinib, le baricitinib, l'upadacitinib ou le ruxolitinib, représentent une nouvelle classe de petites molécules actives sur des cibles intra-cellulaires spécifiques, utilisables par voie orale pour traiter des maladies autoimmunes ou néoplasies myéloprolifératives. Leur efficacité thérapeutique remarquable est contrebalancée par un risque significatif de toxicités essentiellement dose-dépendantes et un profil pharmacocinétique variable. Les JAKi constituent une nouvelle arme thérapeutique pour le traitement des maladies autoimmunes, myéloprolifératives et inflammatoires (Covid-19), mais nécessitent une individualisation et un suivi attentifs. Le suivi thérapeutique des médicaments des JAKi pourrait permettre de personnaliser leur prescription et améliorer leur profil efficacité-toxicité.

Idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome mimicking symptoms of polymyalgia rheumatica: a case report.

BACKGROUND: Remitting seronegative symmetrical synovitis with pitting edema is a rare rheumatic condition of the elderly population that is well described but whose mechanisms remain little studied. This syndrome is characterized by symmetrical swelling located mainly on the dorsal part of the hands and the feet. Because of possible heterogeneous clinical presentation, it can easily mimic the onset of other rheumatic diseases or appear associated with them. Here we report a case of a patient who developed remitting seronegative symmetrical synovitis with pitting edema with preexisting shoulder and hip girdle pain associated with progressive fatigue, indicating a possible differential diagnosis of polymyalgia rheumatica. We reviewed and compared classification for remitting seronegative symmetrical synovitis with pitting edema and polymyalgia rheumatica and discussed other differential diagnoses. CASE PRESENTATION: An 84-year-old Caucasian woman presented to our General Medicine Unit with acute onset of symmetrical hands and feet edema, leading to functional limitation due to pain and stiffness. Additionally, she was complaining about neck, shoulder, and pelvic girdle pain present for about 2 months associated with worsening asthenia. Blood tests showed an elevated level of C-reactive protein and erythrocyte sedimentation rate, as well as absence of anti-cyclic citrullinated peptide antibodies and rheumatoid factor. As all criteria of remitting seronegative symmetrical synovitis with pitting edema syndrome were present, the patient was treated with low-dose prednisone, with a rapid and complete resolution of symptoms. She remains asymptomatic without treatment 2 years after the onset of symptoms, without any evident oncologic etiology. CONCLUSIONS: This case is an example of a classic representation of remitting seronegative symmetrical synovitis with pitting edema syndrome with clinical elements suggesting a concomitant existing early stage of polymyalgia rheumatica. These two entities, classified in the group of seronegative arthritis, can coexist (up to 10% of cases), with remitting seronegative symmetrical synovitis with pitting edema appearing as an initial or late manifestation of polymyalgia rheumatica. It is essential to remind that remitting seronegative symmetrical synovitis with pitting edema is associated with a higher risk of cancer (30%). A proper diagnosis allows the clinician to precisely define the appropriate therapy duration to limit its side effects in the elderly and remain aware of the potential risk of underlying malignancy.

[Use of clinical scores for rheumatoid arthritis and inflammatory rheumatic diseases in routine care]. / Utilité des scores pour le suivi de la polyarthrite rhumatoïde et autres arthropathies inflammatoires.

Many clinical scores have been developed in research to measure rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) activity. In routine care, they may be used as part of a treat to target (T2T) strategy consisting of a systematic evaluation of disease activity followed by an adaptation of the treatment in order to reach a predefined therapeutic target, generally remission. The benefits of this strategy have been showed in RA and its use is recommended for this condition. The added value of the T2T strategy for SpA and PsA remains debated, requiring further studies. Scores may be used for the follow-up of patients, but their limitations should be taken in consideration.

De nombreux scores cliniques ont été développés en recherche pour mesurer l'activité de la polyarthrite rhumatoïde (PR), de la spondylarthrite (SpA) et de l'arthrite psoriasique (PsA). Ils peuvent être utilisés en pratique dans l'application de la stratégie « Treat to Target ¼ (T2T) consistant en une évaluation systé matique de l'activité de la maladie suivie d'une adaptation du traitement afin d'atteindre un objectif thérapeutique prédéfini, généralement la rémission. Les bénéfices de cette stratégie étant démontrés dans la PR, son utilisation est recommandée pour cette pathologie. L'apport de la stratégie T2T pour la SpA et la PsA reste débattu, nécessitant des études complémentaires. L'utilisation d'un score dans le suivi individuel d'un patient peut être utile mais doit se faire avec discernement en connaissance des limites du score.

Efficacy of anakinra in acute hydroxyapatite calcification-induced joint pain: A retrospective study of 23 cases.

OBJECTIVE: Hydroxyapatite (HA) crystal calcifications in or around the joint can induce acute flares with severe pain. A previous pilot study suggested that the interleukin-1ß (IL-1ß) inhibitor anakinra was effective. The goal of this observational study was to confirm these results in a larger set of patients and to report on the long-term follow-up. METHODS: Flare was defined as acute pain for<10 days. Calcification in or around a joint (rotator cuff: 15/23 patients) was confirmed by conventional radiography and/or ultrasonography (US). Anakinra 100mg daily was administered subcutaneously for 1 to 3 consecutive days. Clinical data collected before the injection and on days 3 and 21 included pain score on a visual analog scale (VAS, 0-10cm) and C-reactive protein (CRP) level. When available, US baseline and follow-up findings were compared. Long-term follow-up data were collected from patient charts and/or after a phone call. RESULTS: 23 patients (15 males, mean [SD] age 58 [11] years) were included. Baseline mean (SD) VAS pain was 7.7 (1) cm and CRP level was elevated in half of the patients. After therapy, mean (SD) VAS pain score decreased rapidly in the first 3 days to 1.6 (1.4) cm (P<0.001) and remained stable for 3 weeks at 1.8 (2.1) cm. US assessment revealed decreased Doppler intensity but no significant change in size of calcifications. No significant side effects were noted. After long-term follow-up (median duration 24 months), half of the patients still had some chronic pain, but only 4 experienced acute relapse. CONCLUSION: This study suggests that IL-1ß inhibition may be an efficient therapeutic approach for acute HA flare, with a good safety profile.

The role of IL-1 in gout: from bench to bedside.

The translation of our knowledge of the biology of MSU crystal-induced IL-1 secretion gives rise to new targets and therapeutic strategies in the treatment of acute gout. The NACHT, LRR and PYD domains-containing protein 3 inflammasome is key to this, and is the subject of intense research. Novel pathways that modulate inflammasome activation, reactive oxygen species generation and extracellular processing of IL-1 have been described and show promise in in vitro and animal studies. Meanwhile, blocking IL-1 by various IL-1 inhibitors has shown the validity of this concept. Patients with acute gout treated with these inhibitors showed positive clinical and biological responses. More work needs to be performed to assess the risk/benefit profile of anti-IL-1 therapies as well as to identify those who will benefit the most from this novel approach to the treatment of gout.

[Spondylarthropathies: conventional treatments and anti-TNF]. / Spondyloarthropathies: traitements conventionnels et anti-TNF.

Non-steroidal anti-inflammatory drugs (NSAID) are the first line treatment for spondylarthritis. NSAIDs are effective when used continuously or on demand, in short or long-term use. An effect on radiologic progression of the spine is still controversial. However, physicians have to be aware of potential cardiovascular, renal or gastro-intestinal secondary effects when prescribing NSAIDs. DMARDs like methotrexate or systemic corticosteroids are generally not recommended for the treatment of spondylarthritis. After NSAIDs failure, a TNF inhibitor can be used. 5 anti-TNF are available in Switzerland and they are all effective in this disease. Before starting an anti-TNF treatment, a screening is mandatory. Patients treated with an anti-TNF must be followed regularly.