An investigation of the differential therapeutic effects of romosozumab on postmenopausal osteoporosis patients with or without rheumatoid arthritis complications: a case-control study.

The impact of ROMO on the width of anabolic windows and the increase in BMD was reduced in the RA group compared to the non-RA group, and this reduction was associated with correlations to RA-related factors. PURPOSE: To investigate the effects of romosozumab (ROMO) in postmenopausal osteoporosis, with and without comorbid rheumatoid arthritis (RA). METHODS: In this retrospective, case-controlled, multicenter study, 171 postmenopausal patients who did not receive oral glucocorticoid, comprising 59 in the RA group and 121 in the non-RA group, received uninterrupted ROMO treatment for 12 months. Propensity score matching was employed to ensure comparability in clinical backgrounds, resulting in 41 patients in each group. Baseline characteristics were as follows: overall (mean age, 76.3 years; T-score of lumbar spine (LS), - 3.0; 45.1% were treatment-naive for osteoporosis); RA group (anti-cyclic citrullinated peptide antibody (ACPA) positivity, 80.5%; titer, 206.2 U/ml; clinical disease activity index (CDAI), 13.6; health assessment questionnaire disability index (HAQ-DI), 0.9). Bone mineral density (BMD) and serum bone turnover markers were monitored over a 12-month period. RESULTS: The rate of increase in the bone formation marker, PINP, and the rates of decrease in the bone resorption marker, TRACP-5b, exhibited a trend toward smaller changes in the RA group compared to the non-RA group, implying a smaller anabolic window. After 12 months, the RA group displayed lower BMD increases in the LS (9.1% vs. 12.6%; P = 0.013) and total hip (2.4% vs. 4.8%; P = 0.025) compared to the non-RA group. Multiple regression analysis in the all RA group (n = 59) for the association between RA-specific factors and 12-month BMD changes revealed negative correlations between ACPA titer and LS BMD and between HAQ-DI and femoral neck BMD. CONCLUSIONS: The efficacy of ROMO may be attenuated by RA-related factors.

Early full weight-bearing and gait exercise after cemented total ankle arthroplasty with a modified anterolateral approach.

OBJECTIVES: According to the conventional postoperative procedure after total ankle arthroplasty (TAA), mobilization and weight-bearing is currently started after completion of wound healing. Recently, early mobilization for dorsiflexion after TAA with modified antero-lateral approach was reported to be feasible and safe. To investigate the further possibility of expediting rehabilitation, this study evaluated the feasibility and safety of early full weight-bearing and gait exercise after cemented TAA. MATERIALS AND METHODS: This retrospective, observational study investigated 23 consecutive ankles (OA: 14 ankles, RA: 9 ankles) that had received cemented TAA with a modified antero-lateral approach. These ankles were divided into three groups 1. conventional postoperative protocol, 2. early dorsiflexion protocol, 3. early dorsiflexion+full weight-bearing protocol. Postoperative wound complications were observed and recorded. Number of days for hospitalization was also evaluated. RESULTS: No postoperative complications related to wound healing were observed even after early full weight-bearing and gait exercise. Days for hospitalization was significantly shortened in early full weight-bearing and gait exercise group (group 3) from 35-38 days to 24 days. CONCLUSIONS: Within this small number of cases, early full weight-bearing and gait exercise from 7 days after cemented TAA was feasible and safe with the modified antero-lateral approach. Combination of early dorsiflexion mobilization and weight-bearing/gait exercise contributed to shortening the hospitalization day. Innovations in postoperative procedures for rehabilitation after TAA can be expected.

Associations of disease duration and anti-citrullinated peptide antibody status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis: Post hoc analysis of a multicentre, real-world observational study in Japan (ORIGAMI).

OBJECTIVES: The aim of the article is to investigate the associations of disease duration and anti-cyclic citrullinated peptide antibody (ACPA) status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis (RA). METHODS: We performed post hoc analyses of the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study of biologic-naïve RA patients aged ≥20 years with moderate disease activity who were prescribed abatacept. Changes in the Simplified Disease Activity Index (SDAI) and Japanese Health Assessment Questionnaire (J-HAQ) at 4, 24, and 52 weeks of treatment were analysed in patients divided according to ACPA serostatus (positive/negative), disease duration (<1/≥1 year), or both. RESULTS: SDAI scores decreased from baseline in all groups. SDAI scores tended to decrease more in the ACPA-positive group and disease duration <1-year group than in the ACPA-negative group and disease duration ≥1-year group, respectively. In the disease duration <1-year group, SDAI tended to decrease more in the ACPA-positive group than in the ACPA-negative group. Disease duration was independently associated with the change in SDAI and SDAI remission at Week 52 in multivariable regression models. CONCLUSIONS: These results suggest that starting abatacept within 1 year of diagnosis was associated with greater effectiveness of abatacept in biologic-naïve patients with RA and moderate disease activity.

Baseline serum PINP level is associated with the increase in hip bone mineral density seen with Romosozumab treatment in previously untreated women with osteoporosis.

Baseline serum PINP value was significantly and independently associated with the increased bone mineral density (≥ 3%) in both total hip and femoral necks by 12 months of romosozumab treatment in patients with treatment-naive postmenopausal osteoporosis. PURPOSE: Some patients fail to obtain a sufficiently increased hip bone mineral density (BMD) by romosozumab (ROMO) treatment. This study aimed to investigate the prognostic factor for increased hip BMD with ROMO in patients with treatment-naive postmenopausal osteoporosis. METHODS: This prospective, observational, and multicenter study included patients (n = 63: mean age, 72.6 years; T-scores of the lumbar spine [LS], - 3.3; total hip [TH], - 2.6; femoral neck [FN], - 3.3; serum type I procollagen N-terminal propeptide [PINP], 68.5 µg/L) treated by ROMO for 12 months. BMD and serum bone turnover markers were evaluated at each time point. A responder analysis was performed to assess the patient percentage, and both univariate and multivariate analyses were performed to investigate the factors associated with clinically significant increased BMD (≥ 3%) in both TH and FN. RESULTS: Percentage changes of BMD from baseline in the LS, TH, and FN areas were 17.5%, 4.9%, and 4.3%, respectively. In LS, 96.8% of patients achieved ≥ 6% increased LS-BMD, although 57.1% could not achieve ≥ 3% increased BMD in either TH or FN. Multiple regression analysis revealed that only the baseline PINP value was significantly and independently associated with ≥ 3% increased BMD in both TH and FN (p = 0.019, 95% confidence interval = 1.006-1.054). The optimal cut-off PINP value was 53.7 µg/L with 54.3% sensitivity and 92.3% specificity (area under the curve = 0.752). CONCLUSIONS: In a real-world setting, baseline PINP value was associated with the increased BMD of TH and FN by ROMO treatment in treatment-naive patients.

Early mobilization of dorsiflexion from 3 days after cemented total ankle arthroplasty with modified antero-lateral approach.

BACKGROUND: According to the conventional postoperative procedure after total ankle arthroplasty (TAA), mobilization is currently started after completion of wound healing. To investigate the possibility of expediting rehabilitation, this study evaluated the feasibility and safety of early mobilization of dorsiflexion after cemented TAA utilizing a modified antero-lateral approach. MATERIALS AND METHODS: This retrospective, observational study investigated 14 consecutive ankles that had received cemented TAA. Mobilization of dorsiflexion was started from 3 days after surgery. Postoperative wound complications including blister formation, eschar formation, wound dehiscence, peri-incisional decreased sensation were observed and recorded. Range of motion (ROM) of dorsiflexion/plantar flexion was measured. Patients also completed a self-administered foot evaluation questionnaire (SAFE-Q) and the scale of Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot score preoperatively and at final follow-up. RESULTS: No postoperative complications related to wound healing were observed. ROM for dorsiflexion, SAFE-Q score, and JSSF score improved significantly after TAA. CONCLUSION: Within this small number of cases, early mobilization of dorsiflexion from 3 days after cemented TAA was feasible and safe with the modified antero-lateral approach. Innovations in postoperative procedures for rehabilitation after TAA can be expected.

Low serum albumin concentration is associated with increased risk of osteoporosis in postmenopausal patients with rheumatoid arthritis.

BACKGROUND: The risk of osteoporosis in patients with rheumatoid arthritis (RA) is frequently overlooked, and investigating a simple indicator in routine care may be beneficial to motivate osteoporosis examination. The aim of this retrospective, case-controlled study was to identify the correlation between serum albumin concentrations and the prevalence of osteoporosis in postmenopausal patients with RA. METHODS: This study enrolled 197 patients who underwent dual-energy X-ray absorptiometry of lumbar spine (LS) and proximal femur without osteoporosis treatment [mean age, 67.5 years; disease duration, 12.8 years; Disease Activity Score assessing 28 joints with C-reactive protein, 2.0; prednisolone dose, 4.9 mg/day (usage, 42.6%); and LS T-score, -1.9]. Patients were classified into 2 groups: osteoporosis, defined as ≥ 1 part bone mineral density T-score ≤ -2.5 or history of fragility fracture of the vertebra or proximal femur (121 patients), and non-osteoporosis (76 patients). Groups were then matched by propensity score using clinical backgrounds affecting bone metabolism. RESULTS: In non-matched model, serum albumin concentration was significantly associated with osteoporosis-related factors such as aging, inflammation, physical disability, and glucocorticoid dose. Multivariate logistic regression revealed that serum albumin concentration was independently and significantly associated with osteoporosis risk (odds ratio = 0.22, 95% confidence interval = 0.08, 0.61, p = 0.0033). After propensity score matching, 57 patients for each group showed that in addition to the LS and femoral neck T-scores (p < 0.001), serum albumin concentrations (p = 0.01) remained lower in the osteoporosis group compared to non-osteoporosis group. Receiver operating characteristic curve analysis in non-matched model revealed that when cut-off value of serum albumin concentration for indicating osteoporosis was set at 4.2 g/dl, the area under the curve was 0.69, sensitivity 0.74, and specificity 0.58. CONCLUSIONS: Low serum albumin concentration was significantly and independently associated with the prevalence of osteoporosis, which may be considered as one of the osteoporosis-related factors in postmenopausal patients with RA.

Effects of follow-on therapy after denosumab discontinuation in patients with postmenopausal osteoporosis.

OBJECTIVES: To clarify the effects of follow-on therapy after denosumab (DMAb) discontinuation. METHODS: In this retrospective, multicenter study, postmenopausal patients with osteoporosis who were previously treated by oral bisphosphonates (BP) (n = 26) or teriparatide (TPTD) (n = 27) were switched to DMAb (administered 2.6 times), and then discontinued. Patients (73.1 years, T-scores of the lumbar spine [LS] - 2.7 and femoral neck [FN] - 2.2) were switched to either (1) raloxifene (RAL) (n = 13) or BP [(2) weekly or monthly BP (wmBP) (n = 29) or (3) zoledronate (ZOL) (n = 11)], based on each physician's decision (mean interval after final DMAb administration was 7.2 months). Bone mineral density (BMD) at final DMAb administration were set as baseline. RESULTS: Changes in LS BMD at 1.5 years after final DMAb administration were -2.7% in the RAL, 0.7% in the wmBP, and 1.9% in the ZOL (p = .31 between groups), and in FN BMD were -3.8%, -0.8%, and 1.8%, respectively (p = .02 between the RAL and ZOL; p = .048 between the RAL and BP). Clinical vertebral fracture incidence during 1.5 years after final DMAb administration was 23.1% in the RAL, 3.4% in the wmBP, and 0.0% in the ZOL (p = .048 between the RAL and ZOL; p = .015 between the RAL and BP). No significant differences were observed in these parameters between the wmBP and ZOL. CONCLUSION: These results may contribute to the selection of adequate follow-on therapy after DMAb discontinuation, although further investigations are required.

Anti-receptor activator of nuclear factor κB ligand antibody treatment increases osteoclastogenesis-promoting IL-8 in patients with rheumatoid arthritis.

The receptor activator of nuclear factor κB ligand (RANKL) is an important factor for osteoclastogenesis and contributes to the pathology of rheumatoid arthritis (RA); thus, the anti-RANKL antibody (Ab) has been expected to protect joint destruction in RA patients. IL-8 also has osteoclastogenic activity; however, the role of IL-8 in the bone pathology of RA as well as the relation between IL-8 and RANKL remain unclear. In the present study, clinical observation revealed serum IL-8 levels of 611 pg ml-1 in RA patients with anti-RANKL Ab and 266 pg ml-1 in the same patients without anti-RANKL Ab. In vitro assay showed that anti-RANKL Ab induced production of IL-8 from pre-osteoclast-like cells (OCLs), and IL-8 promoted the formation of OCLs from peripheral monocytes even without RANKL activity. We further showed that treatment with FK506 (tacrolimus) possibly inhibits the increase in IL-8 levels in RA patients with anti-RANKL Ab, and in vitro assay confirmed that FK506 suppressed IL-8 production in pre-OCLs. These results suggest that inhibition of RANKL induces the change in osteoclastogenesis-promoting factor from RANKL to IL-8, and FK506 may be a valuable combination drug to support the use of anti-RANKL Ab in treatment of RA.

Radiographic effects observed in the coronal view after medial malleolar osteotomy at total ankle arthroplasty in rheumatoid arthritis cases.

BACKGROUND: When soft tissue balance is not acceptable at total ankle arthroplasty (TAA) for rheumatoid varus deformity, medial malleolar osteotomy has been performed. At the same time, the shape of the ankle joint changes after soft tissue balancing with such an osteotomy, however there is few information for the radiographic findings after the osteotomy. Thus, radiographic changes in the coronal view of such cases were investigated. METHODS: JSSF-RA foot and ankle scale and SAFE-Q scores were determined along with pre/postoperative radiographic parameters of the ankle joint in 70 ankles (65 patients) with rheumatoid arthritis followed for a mean of 7.9 years (range, 2-16 years) after TAA. Seven ankles were excluded because those underwent lateral or lateral/medial malleolar osteotomy. Twenty-seven ankles underwent medial malleolar osteotomy, and compared with 36 ankles without osteotomy. RESULTS: All ankles achieved bone union after medial malleolar osteotomy, and the tibial medial malleolus (TMM) angle was significantly decreased [30.3°-19.1°] following significant valgus correction [TC angle: -2.7° to 0.5°]. The gap due to medial soft tissue tightness was significantly improved by medial malleolar osteotomy [4.95° to 0.7°]. Lateral malleolar fractures sometimes occurred (19%: 5/27 ankles) at valgus correction, but they healed completely without any internal fixation. CONCLUSION: Medial malleolar osteotomy was useful in rheumatoid varus ankle for not only controlling the soft tissue balance, but also providing a stabilized shape of the ankle joint. Lateral malleolar fractures were caused by valgus correction following medial malleolar osteotomy in some cases, but all fractures were completely healed without any internal fixation.

Effects of range of motion exercise of the metatarsophalangeal joint from 2-weeks after joint-preserving rheumatoid forefoot surgery.

Objectives: Joint-preserving rheumatoid forefoot surgery improves clinical outcomes, but postoperative range of motion (ROM) of the metatarsophalangeal (MTP) joint remains an issue. The objective of this study was to evaluate the effect of ROM exercise from the early period after lesser toe MTP joint-preserving surgery.Methods: A retrospective, observational study of 22 rheumatoid arthritis patients who underwent modified metatarsal shortening offset osteotomy was completed. Lesser toe scales were administered using the Japanese Society for Surgery of the Foot (JSSF) standard rating system, and the maximum distance of continuous walking was checked to evaluate clinical outcomes. Maximum passive ROM of the lesser toe MTP joints and the extension angle of the 2nd MTP joint at the terminal stance phase during gait were measured and evaluated.Results: Pain scores and ROM-related indices of the JSSF lesser toe scale improved significantly in the exercise group. The extension angle of the 2nd MTP joint at the terminal stance phase during gait was increased, and the maximum distance of continuous walking seemed longer.Conclusion: Passive/active ROM exercise from 2-weeks after surgery can improve a patient's activity and forefoot function through increasing ROM of the MTP joint at the terminal stance phase.

Impact of combining medial capsule interposition with modified scarf osteotomy for hallux valgus.

Objectives: To clarify the effect of combining medial capsule interposition with modified scarf osteotomy for hallux valgus.Methods: A multicenter, retrospective study included 64 cases [59 osteoarthritis patients (excluding rheumatoid arthritis); age 68.8 years, range 40-93 years] of modified scarf osteotomy which were performed from 2013 to 2017 and followed for 26.6 (range, 13-50) months. Patients were treated by either (1) without medial capsule interposition (33 cases) or (2) combined with interposition (31 cases) at each senior surgeon's discretion. The Japanese Society for Surgery of the Foot (JSSF) hallux metatarsophalangeal (MTP)-interphalangeal scale was evaluated along with radiographic parameters (hallux valgus angle [HVA], first and second metatarsals intermetatarsal angles, and Hardy grade).Results: All JSSF scale and radiographic parameters were similar at baseline and significantly improved at final follow-up in both groups (pre-operation vs. final follow-up: p < .001). However, compared to without interposition group, interposition group showed significantly higher improvement in the JSSF scale (pre-operation to final follow-up: p value between the two groups at final follow-up) for pain (without interposition: 19.4-34.2, interposition: 18.4-37.1; p = .02), function (without interposition: 20.8-33.6, interposition: 18.3-36.6; p = .005), total score (without interposition: 41.5-81.8, interposition: 38.5-88.5; p < .001), and the MTP joint space (without interposition: 1.4-1.5 mm, interposition: 1.6-2.6 mm; p < .001) with significant correlation between the total JSSF score (r = .40; p = .001).Conclusion: Combining medial capsule interposition with modified scarf osteotomy significantly improved mid-term clinical outcomes.

Appearance of hindfoot valgus deformity and recurrence of hallux valgus in the very early period after hallux valgus surgery in a poorly controlled rheumatoid arthritis case: A case report.

Control of rheumatoid arthritis (RA) disease activity is an important factor related to the development of hallux valgus (HV) deformity. Furthermore, if valgus hindfoot remains and/or appears after HV surgery, the affected foot is at risk of recurrence of HV deformity. We experienced a case suggesting the possibility that hindfoot valgus deformity appeared after HV surgery because of poor control of RA disease activity, and the HV deformity recurred in the very early period after surgery.

Nurse-like cells in rheumatoid arthritis: Formation of survival niches cooperating between the cell types.

Nurse-like cells (NLCs) established from bone marrow and synovial tissue of rheumatoid arthritis (RA) patients were found to promote maturation and differentiation of B lineage cells as well as T cells. In co-culture of RA-NLCs and B cells, tight physical interactions (pseudoemperipolesis) developed, which resulted in activation of both cell types. RA-NLCs also supported myeloid cell maturation, promoting their differentiation into tartrate-resistant acid phosphatase-positive mononuclear cells, which are precursor cells of osteoclasts. In RA synovial tissue, the characteristic dendritic-shaped cells (the DCs) were electron microscopically found to form direct physical interactions with adjacent plasma cells (PCs) suspecting to be pseudoemperipolesis. The numbers of PCs accumulating in various areas tended to correlate with the numbers of the DCs, which appeared to have RA-NLC functions forming survival niches for PCs. Immunohistochemical staining analysis indicated that CD14+ cells including the DCs formed survival niches for CD138+ PCs by RA-NLC functions. Quantitative dual immunofluorescence staining studies of these areas indicated that the majority of CD14+ cells were of myeloid lineage. These survival niches promoted by RA-NLCs appear to play important roles in supporting immunological functions in RA bone marrow and synovial tissues.

The add-on effectiveness and safety of iguratimod in patients with rheumatoid arthritis who showed an inadequate response to tocilizumab.

Objectives: To evaluate the effectiveness of add-on iguratimod (IGU) in patients with rheumatoid arthritis (RA) who showed an inadequate response to tocilizumab (TCZ), especially patients who were intolerant of an effective dose of methotrexate (MTX). Methods: Thirty-one patients with RA (22 women, age 62.4 years, disease duration 13.8 years, prior TCZ duration 35.7 months, 25 intravenous [8 mg/kg/4 weeks] and 6 subcutaneous [162 mg/2 weeks] TCZ treatments, concomitant MTX 8.5 mg/week [35.5%], and prednisolone (PSL) 4.3 mg/day [25.8%]) who showed an inadequate response to TCZ (disease activity score assessing 28 joints with C-reactive protein [DAS28-CRP] 2.9, clinical disease activity index [CDAI] 15.0, 28 secondary inadequate responders) were treated with additional IGU (final dose 41.7 mg/day) and enrolled in this 24-week, multicenter, retrospective study. Results: Twenty-nine patients (93.5%) continued the treatment for 24 weeks (one dropped out for pneumonia and one for digestive symptoms). The TCZ and the concomitant dose and rate of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (MTX, salazosulfapyridine [SASP], and tacrolimus [TAC]) were not significantly changed during this period. Outcome measures improved significantly, as follows: DAS28-CRP from 2.9 to 1.7 (p < .001); CDAI from 15.0 to 6.0 (p < .001); modified Health Assessment Questionnaire (mHAQ) from 0.8 to 0.6 (p < .05); and rheumatoid factor (RF) from 382.1 to 240.3 IU/mL (p < .001). Using the EULAR criteria, 64.5% achieved a moderate response, and 51.6% achieved ACR 20 at 24 weeks. Conclusion: Adding IGU to inadequate responders to TCZ may be a promising and safe complementary treatment option.

Hallux valgus deformity after total ankle arthroplasty for rheumatoid arthritis: A case report.

Hallux valgus (HV) deformity is associated with hindfoot valgus deformity. We experienced a case that suggests the possibility that valgus correction for varus hindfoot with bony ankylosis of the subtalar joint by total ankle arthroplasty may have caused a forefoot HV deformity, despite adequate valgus correction.

Association between preoperative pain intensity of MTP joint callosities of the lesser toes and fore-mid-hindfoot deformities in rheumatoid arthritis cases.

OBJECTIVES: To determine whether preoperative pain intensity in callosities of the lesser toe metatarsopharangeal (MTP) joint was associated with the grade of fore-mid-hindfoot deformities, because rheumatoid arthritis (RA) foot deformity includes the whole part of foot, and curiously differences between cases in the pain intensity of MTP joint callosities are often observed. METHODS: We evaluated 24 feet that had undergone forefoot surgery [August, 2014 - December, 2015] for painful lesser toe MTP joint deformity (callosities) in RA cases. A preoperative self-administered foot evaluation questionnaire (SAFE-Q) and pressure distribution information for foot function were also investigated. X-rays of the whole lower extremities and foot at weight-bearing were used to check fore-mid-hindfoot deformities. RESULTS: Group M (mild) [n = 9] included patients with the pain visual analog scale (VAS) less than 40 mm, while group S (severe) [n = 15] included patients whose VAS was over 40 mm. Group M showed stronger hindfoot valgus and pronated (abducted) deformity, and group M showed higher pressure on the first MTP joint compared with group S. CONCLUSIONS: These observations reconfirm that hindfoot valgus deformity and/or pronated (abducted) foot deformity affects the forefoot loading distribution, subsequently the pain of callosities in lesser toe MTP joints could be decreased.

Outcomes of modified metatarsal shortening offset osteotomy for forefoot deformity in patients with rheumatoid arthritis: Short to mid-term follow-up.

OBJECTIVES: Advances in drug therapy for rheumatoid arthritis (RA) have been encouraging us to preserve the metatarsopharangeal (MTP) joint in correction of forefoot deformities, and original metatarsal shortening offset osteotomy was recommended as one of the conventional surgical options for forefoot deformities in RA cases. The objective of this study was to evaluate short- to mid-term outcomes of modified metatarsal shortening offset osteotomy. METHODS: A retrospective observational study was completed for 80 RA cases (mean follow-up period: 3.2 years) who underwent modified metatarsal shortening offset osteotomy. Both lesser toe scales and RA foot ankle scales were administered using the Japanese Society for Surgery of the Foot (JSSF) standard rating system, and a postoperative self-administered foot evaluation questionnaire (SAFE-Q) at final follow-up was also checked to evaluate clinical outcomes. RESULTS: This procedure significantly improved clinical scores of both the JSSF [lesser toes and RA foot and ankle] scales. Of 80 feet, 24 (30%) showed recurrence of MTP joint subluxation/dislocation. Furthermore, the feet in the recurrence group showed significant varus hindfoot. On the other hand, valgus foot in the recurrence group more frequently included midfoot bony ankyloses. All of the affected feet showed the limitation of MTP joints (<70°) after surgery. CONCLUSIONS: Modified metatarsal shortening offset osteotomy was recommended for RA forefoot disorders as one of the joint preservation surgeries in short- to mid-term follow-up. However, some modifications to avoid limitation of ROM in the MTP joint are required. It must be borne in mind that varus hindfoot and/or bony ankyloses in the mid-hindfoot can cause recurrence of dorsal dislocation/subluxation of the lesser toe MTP joint.

The efficacy and safety of additional administration of tacrolimus in patients with rheumatoid arthritis who showed an inadequate response to tocilizumab.

OBJECTIVES: Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown. METHODS: Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI] ≥ 5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study. RESULTS: Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p < 0.001), CDAI from 17.7 to 7.6 (p < 0.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p < 0.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP ≤2.7 or CDAI ≤10) at week 24. CONCLUSIONS: Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option.