Efficacy and safety of risankizumab for Crohn's disease in patients from Asian countries: a post hoc subanalysis of the global phase 3 ADVANCE, MOTIVATE, and FORTIFY studies.

BACKGROUND AND AIM: The anti-interleukin-23 antibody risankizumab is being investigated as a treatment for moderate-to-severe Crohn's disease. This post hoc subanalysis evaluates the efficacy and safety of risankizumab therapy in Asian patients. METHODS: ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) were randomized, double-blind, placebo-controlled, phase 3 induction studies. Patients with intolerance/inadequate response to biologic (MOTIVATE) and/or conventional therapy (ADVANCE) were randomized to receive intravenous risankizumab (600 or 1200 mg) or placebo at weeks 0, 4, and 8. Clinical responders to risankizumab could enter the phase 3, randomized, double-blind, placebo-controlled maintenance withdrawal study (FORTIFY; NCT03105102). Patients were rerandomized to receive subcutaneous risankizumab (180 or 360 mg) or placebo (withdrawal) every 8 weeks for 52 weeks. RESULTS: Among 198 Asian patients in the induction studies, clinical remission and endoscopic response at week 12 were achieved by 61.4% and 40.0%, 59.5% and 35.8%, and 27.3% and 9.1% of patients in the risankizumab 600 mg, risankizumab 1200 mg, and placebo groups, respectively. Among 67 patients who entered the maintenance study, clinical remission and endoscopic response at week 52 were achieved by 57.1% and 52.4%, 75.0% and 40.0%, and 53.8% and 34.6% of patients in the risankizumab 180 mg, risankizumab 360 mg, and placebo (withdrawal) groups, respectively. Fistula closure was observed with risankizumab treatment in 28.6% (induction) and 57.1% (maintenance) of patients. Efficacy trends and safety profile were similar to those in non-Asian patients. CONCLUSION: Consistent with non-Asian and global population results, risankizumab was effective and well tolerated in Asian patients with Crohn's disease.

Neglected spontaneous rupture of the Achilles tendon in elderly patients with rheumatoid arthritis.

Spontaneous Achilles tendon rupture associated with rheumatoid arthritis (RA) is a very rare complication. In this report, we have experienced neglected spontaneous rupture of the Achilles tendon in 5 elderly RA patients, and report its clinical features and management. These patients had taken corticosteroids for a long time for RA control. Moreover, they did not show any signs, such as click or impact on the rear foot at the moment of the rupture, and had few complaints or obvious symptoms around their ankles or the rear of the foot after the rupture. This suggests that the lack of severe symptoms prevented the early diagnosis of the Achilles tendon rupture, and that this injury had been neglected during treatment for RA. Therefore, careful diagnosis of the Achilles tendon rupture is needed in elderly patients with RA, even if they have little or no history of trauma.

Prediction of wrist prognosis in patients with early rheumatoid arthritis according to radiographic classification.

PURPOSE: We conducted a prospective study of patients with recent-onset rheumatoid arthritis to determine the importance of carpal height ratio (CHR) or ulnar translation ratio (UTR) in predicting radiographic progression of rheumatoid arthritis in the wrist, especially with regard to stable or progressive wrist arthritis. METHODS: We evaluated 106 wrists with early rheumatoid arthritis. Radiologic misalignment was assessed by measuring CHR and UTR. The modified Schulthess classification of rheumatoid wrist involvement was used to classify the subtypes of wrist joint destruction radiographically types I, II, III, and IV, defined as ankylosing, osteoarthritis, disintegrating, and normal, respectively. We evaluated the wrist joints as stable or progressive by measuring the values of CHR and UTR indices. We also examined whether the modified Schulthess classification of rheumatoid wrist involvement subtypes are associated with radiographic progression over 10 years using the baseline CHR and UTR indices. RESULTS: The mean CHR values of types I and III were 0.42 (95% confidence interval [CI], 0.40-0.43) and 0.37 (95% CI, 0.34-0.39), respectively. The mean UTR values of types I and III were 0.348 (95% CI, 0.336-0.360) and 0.351 (95% CI, 0.339-0.367), respectively. These values indicated that degradation was faster in types I and III than in other types. We then found type I and III wrists to have progressive arthritis, and type II and IV wrists stable arthritis. We also found that the baseline CHR index was a significant (p < .05) predictor of radiographic progression. CONCLUSIONS: Our results indicated that type I and III wrists had radiographic progression and ultimately underwent deformation. This analysis also showed that the baseline CHR index was even more useful in predicting radiographic progression after 10 years.

Granzyme B induces apoptosis of chondrocytes with natural killer cell-like cytotoxicity in rheumatoid arthritis.

OBJECTIVE: Granzyme B, an apoptosis-inducing factor, is expressed in natural killer (NK) cells, an important factor in innate immunity. We previously reported that granzyme B is expressed in arthritic cartilage and chondrocytes, and suggested that granzyme B expression is related to apoptosis distribution. We have now investigated whether granzyme B directly induces apoptosis in chondrocytes and whether chondrocytes possess NK cell-like function. METHODS: Chondrocytes included the human C-28/12 chondrocyte cell line, normal chondrocytes, and rheumatoid arthritis (RA) chondrocytes. Apoptosis was analyzed by ELISA and TUNEL after C-28/12 cells were incubated with active granzyme B. NK cell markers were examined in chondrocytes by FACS and immunohistochemistry. Chondrocytes with or without Z-AAD-CMK, a known granzyme B inhibitor, were stimulated with PHA (20 microg/ml), followed by coculture with K562 cells in order to test chondrocyte cytotoxity. RESULTS: Granzyme B was successfully introduced into C-28/12 chondrocytes, and was confirmed to dose-dependently induce apoptosis. Immunohistochemically, chondrocytes expressed the surface antigens of NK cells and exhibited cytotoxicity against K562 cells, which served as an indicator of cytotoxicity. Z-AAD-CMK inhibited cytotoxicity against K562 cells in a dose-dependent manner, thus confirming that chondrocyte cytotoxicity against K562 cells is dependent on granzyme B. CONCLUSION: Our findings indicate that chondrocytes possess NK cell-like activity related to innate immunity, and that apoptosis is induced in these cells by granzyme B. Our findings suggest that inflammation activates granzyme B, which participates in the destruction of RA-affected joints.

Disturbances of the symphysis pubis in rheumatoid arthritis: report of two cases.

We present two rheumatoid arthritis (RA) patients suffering from disturbances of the symphysis pubis. Radiography revealed one with pelvic ring disruption with symphysis pubis diastasis, and the other with osteolysis at both pubic rami and disruption of the superior aspect of the symphysis pubis. Both cases had received long-term corticosteroid therapy, including pulse therapy. We recommend reducing the corticosteroid dose to prevent disturbances of the symphysis pubis especially in RA patients on long-term steroid therapy.

Neglected spontaneous rupture of the Achilles' tendon in patients with systemic lupus erythematosus.

Spontaneous Achilles' tendon rupture associated with systemic lupus erythematosus (SLE) is rare complication in literature review. We encountered two patients with neglected spontaneous ruptures of Achilles' tendons who had been on corticosteroid therapy to treat SLE. The ages of these patients were 43 and 49 years, and both were women. One of them was a case of bilateral Achilles' tendons rerupture. Achilles' tendons of both patients were reconstructed by surgery because of delay in their diagnosis. Histological section of the both ruptured Achilles' tendon revealed fibrotic scar tissue and little existence of inflammatory change. We concluded that careful diagnosis, surgical suture, and careful treatment after operation are necessary for Achilles' tendon rupture in those patients with SLE.