Tofacitinib 5 mg Twice Daily in Patients with Rheumatoid Arthritis and Inadequate Response to Disease-Modifying Antirheumatic Drugs: A Comprehensive Review of Phase 3 Efficacy and Safety.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We performed a comprehensive review of phase 3 studies of tofacitinib 5 mg twice daily (BID) (approved dose in many countries) in patients with moderate to severe RA and inadequate response to prior disease-modifying antirheumatic drugs. METHODS: A search of PubMed and ClinicalTrials.gov identified 5 studies: ORAL Solo (NCT00814307), ORAL Sync (NCT00856544), ORAL Standard (included adalimumab 40 mg once every 2 weeks; NCT00853385), ORAL Scan (NCT00847613), and ORAL Step (NCT00960440). Efficacy and safety data for tofacitinib 5 mg BID, placebo, and adalimumab were analyzed. RESULTS: Across the 5 studies, 1216 patients received tofacitinib 5 mg BID, 681 received placebo, and 204 received adalimumab. At month 3, tofacitinib demonstrated significantly higher 20%, 50%, and 70% improvement in American College of Rheumatology response criteria (ACR20, ACR50, and ACR70, respectively) response rates, greater improvement in Health Assessment Questionnaire-Disability Index, and a higher proportion of Disease Activity Score-defined remission than placebo. Frequencies of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar for tofacitinib and placebo at month 3; serious infection events were more frequent for tofacitinib. In ORAL Standard, although not powered for formal comparisons, tofacitinib and adalimumab had numerically similar efficacy and AEs; serious AEs and serious infection events were more frequent with tofacitinib. CONCLUSIONS: Tofacitinib 5 mg BID reduced RA signs and symptoms and improved physical function versus placebo in patients with inadequate response to prior disease-modifying antirheumatic drugs. Tofacitinib 5 mg BID had a consistent, manageable safety profile across studies, with no new safety signals identified.

Seizure and Acute Vision Loss in a Filipino Lupus Patient: A Case of Posterior Reversible Encephalopathy Syndrome with Intraparenchymal Hemorrhage.

Posterior reversible encephalopathy syndrome (PRES) is a rare and poorly understood neurologic condition that has been described in some patients with systemic lupus erythematosus (SLE). Intracerebral hemorrhage is a unique and atypical presentation of PRES and has been described only in a small number of patients with SLE. We present the case of a 33-year-old female, diagnosed with SLE and active nephritis, who was admitted for seizures. She had acute-onset headache, confusion, and bilateral vision loss associated with severe hypertension. CT scan revealed right occipital and parietal lobe hemorrhage. MRI showed vasogenic edema and hyperintense foci in bilateral cortical and subcortical regions of the occipital and posterior parietal lobes which are consistent with posterior reversible encephalopathy syndrome (PRES). Strict blood pressure control and medical ICP-lowering treatment were immediately instituted, while maintaining her on anticonvulsants, high-dose steroids, and mycophenolate mofetil. The patient was discharged with improvement in vision and resolution of headache. On follow-up, she had gained her premorbid visual acuity and reported no recurrence of headache or seizures. Despite its name, reversibility remains to be conditional in PRES. A high index of suspicion is important, especially among those who present with seizure, headache, and visual loss. Early diagnosis and timely initiation of therapy is recommended, as clinical symptoms are potentially reversible and delayed therapy may result in life-threatening complications, such as coma or death.

A case of Churg-Strauss syndrome presenting with foot drop

BACKGROUND: Churg-Strauss syndrome (CSS), or eosinophilic granulomatosis with polyangiitis, is a rare syndrome that affects small- to medium-sized arteries and veins. Criteria for the diagnosis include: asthma (wheezing, expiratory rhonchi), eosinophilia of more than 10% in peripheral blood, paranasal sinusitis, pulmonary infiltrates (may be transient), histological proof of vasculitis with extravascular eosinophils, and mononeuritis multiplex or polyneuropathy. The worldwide incidence of CSS is approximately 2.5 cases per 100,000 adults per year and its incidence in the United States is one to three cases per 100,000 adults per year.1 In the Philippines, the exact incidence is unknown with very few published case reports about it.SETTING: University of the Philippines-Philippine General Hospital (UP-PGH), a tertiary training hospital in Manila, PhilippinesTHE CASE: A 40-year-old Filipino male with a history of adult onset asthma and recurrent sinusitis manifesting with inability to dorsiflex the left ankle (foot drop), various dermatologic lesions, and arthralgia. Complete blood count showed hypereosinophilia. Electromyography revealed asymmetric moderate to severe sensory and motor denervation of limbs compatible with polyneuropathy. Skin biopsy revealed lymphocytic vasculitis. P-ANCA was positive. During his incumbent hospitalization, the skin lesions, arthralgia and neurologic manifestations improved on administration of high dose steroids. Pregabalin was used to control pain secondary to the mononeuritis multiplex.SIGNIFICANCE: To report a rare case of ChurgStrauss syndrome presenting as foot drop. This case highlights the importance of considering ChurgStrauss syndrome among adult patients presenting with neurologic complaint (inability to dorsiflex the left ankle/foot drop) and various dermatologic lesions.

Cardiac tamponade as a rare manifestation of systemic lupus erythematosus: A report on four cases in the Philippine General Hospital

SYNOPSIS: Cardiac tamponade among systemic lupus erythematosus (SLE) patients is an unusual event. The pericardial effusion may be a consequence of uremia, infections in the pericardium, or the lupus pericarditis itself. We present four atypical cases of cardiac tamponade from pericarditis of connective tissue disease (CTD), all of which were treated with drainage and immunosuppressants. Due to the rarity of this combination, management was a challenge.CLINICAL PRESENTATION: Four females each sought consult for dyspnea associated with typical manifestations of connective tissue disease such as arthritis, characteristic rashes, serositis, typical laboratory features, and a positive ANA and/or anti-dsDNA. The first three cases fulfilled the criteria for SLE, while the fourth fulfilled the criteria for SLE-dermatomyositis overlap syndrome. Echocardiography was done due to suspicion of pericardial involvement and revealed massive pericardial effusion in tamponade physiology in all cases.DIAGNOSIS: Cardiac tamponade from serositis due to connective tissue disease [SLE (case 1 to 3) or SLE-dermatomyositis overlap (case 4). Other common etiologies of tamponade such as bacterial, tuberculous, malignant, and uremic pericardial effusion were ruled out by clinical and laboratory tools, including Gram stain and culture, cytology, PCR, and biochemical testing. The pericardial fluid of the first case tested positive for lupus erythematosus (LE) cells, indicative of lupus serositis.TREATMENT AND OUTCOME: All patients underwent pericardial drainage via tube pericardiostomy. They received high dose glucocorticoids after infectious etiologies for the pericardial effusion were ruled out. The fourth case with the overlap syndrome, however, required more immunosuppressants using azathioprine and methotrexate. Resolution of pericardial effusion was noted with this approach. Three of four were discharged improved, however, the third case suffered from worsening nephritis and pulmonary hemorrhage leading to her demise.SIGNIFICANCE AND RECOMMENDATIONS: Four cases of cardiac tamponade as a manifestation of connective tissue disease were presented. Literature underlines the rarity of this condition anytime during the course of SLE. Despite this, SLE should be considered as one of the differential diagnosis of cardiac tamponade, especially in patients who manifest with multi-systemic findings. Likewise, massive pericardial effusion should be considered in patients with a connective tissue disease presenting with subtle evidence of pericardial involvement. It requires timely identification and treatment with high dose steroids, after other causes such as infections have been excluded. Immediate drainage through pericardiocentesis or pericardiostomy in combination with immunosuppressants may be life-saving.